CDK
信号通路图
研究领域
抑制剂选择性比较
特异性亚型抑制剂
CDK产品
| 目录号 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S1116 |
Palbociclib (PD-0332991) HClPalbociclib (PD-0332991) HCl是一种高度选择性的CDK4/6抑制剂，无细胞试验中IC50分别为11 nM/16 nM。它对CDK1/2/5，EGFR，FGFR，PDGFR，InsR等没有抑制活性。Phase 3。 |
Patient tumor cell sensitivity to combinatorial treatment with histone deacetylase (HDAC)/cyclin-dependent kinase (CDK) inhibitors in 3-D culture. The effect of each drug or drug combination was assessed by fluorescent dye to identify live (green) and dead cells (red). Cells from breast reduction patients were used as non-cancer control in the assay. |
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| S1153 |
Roscovitine (Seliciclib,CYC202)Roscovitine (Seliciclib,CYC202)是一种有效的，选择性CDK抑制剂，作用于Cdc2，CDK2和CDK5时，无细胞试验中IC50分别为0.65 μM，0.7 μM和0.16 μM，对CDK4/6几乎没有作用。Phase 2。 |
Inhibition of CDK5 by roscovitine resulted in defective neuronal migration, which was rescued by expression of GFP-Ndel1 (S251E). a, Granular neurons were treated with roscovitine. Western blotting was performed 24 h after start of culture. Aurora-A and NDEL1 displayed similar expression levels with untreated neurons, whereas the levels of phosphorylated Aurora-A and NDEL1 proteins were decreased after treatment with roscovitine. Relative intensities of the bands of Western blotting are shown at the bottom. |
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| S1145 |
SNS-032 (BMS-387032)SNS-032 (BMS-387032)最初被描述为选择性CDK2抑制剂，无细胞试验中IC50为48 nM，比作用于CDK1/CDK4选择性高10和20倍。它也对CDK7/9敏感，IC50为62 nM/4 nM，对CDK6几乎没有抑制效果。 Phase 1。 |
HeLa cells were treated for 3h with PIK-75 or SNS-032 at the indicated concentrations. Cells were subsequently lysed and subjected to western blotting. One representative of two independent experiments is shown.
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| S2768 |
Dinaciclib (SCH727965)Dinaciclib (SCH727965)是一种新型有效的CDK抑制剂，作用于CDK2，CDK5，CDK1和CDK9，无细胞试验中IC50分别为1 nM，1 nM，3 nM和4 nM。它也会阻断胸甘(dThd) DNA整合。Dinaciclib 可通过激活caspases 8和caspases 9来诱导细胞凋亡。Phase 3。 |
CDK4/6 inhibition has potent cytostatic effect in HER2-positive models. The indicated cells were treated with PD-0332991 (1 uM) or Dinaciclib (1 uM) for 96 hours and plates were stained with crystal violet.
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| S1230 |
Flavopiridol (Alvocidib)Flavopiridol (Alvocidib) 与ATP竞争性抑制CDKs，包括CDK1、CDK2、CDK4、CDK6和CDK9的IC50范围为20-100 nM。作用于CDK1、2、4、6、9比作用于CDK7更具有选择性。Flavopiridol最初被发现能抑制EGFR和PKA。Flavopiridol可诱导自噬和内质网应激反应。Flavopiridol可阻滞HIV-1的复制。Phase 1/2。 |
(C) In vivo treatment of Tg:Pomc-Pttg;Pomc-eGFP embryos with small-molecule CDK inhibitors (50 μM) or 0.2% DMSO as control from 18 to 40 hpf. One hundred to one hundred fifty embryos were treated with each compound. Representative images of live embryos are shown with gross morphology (Right) and pituitary Pomc-GFP-positive cells at higher magnification (Left) at 40 hpf. Embryos exposed to flavopiridol developed early developmental defect before pituitary POMC cell ontogeny occurs. (D) Relative expression of pituitary Pomc-eGFP fluorescence analyzed using Volocity 5.2 software (Improvision; mean ±SE of relative expression, n = 7). (E) R-roscovitine specifically suppresses expansion of pituitary POMC cells overexpressing zPttg from 18 to 48 hpf. Double transgenic Tg:Pomc-Pttg;Prl-RFP embryos were generated by breeding Tg:Pomc-Pttg fish with a previously generated PRL-RFP transgenic line, in which RFP was targeted to pituitary lactotrophs by a zebrafish Prolactin promoter (34). Representative fluorescent microscopy of pituitary POMC-eGFP (a and b) and PRL-RFP (c and d) expression in live Tg:Pomc-Pttg; Pomc-eGFP and Tg:Pomc-Pttg;Prl-RFP embryos treated with 0.2% DMSO (a and c) or 50 μM R-roscovitine (b and d). (F) Relative expression of pituitary POMC-eGFP or PRL-RFP fluorescence were analyzed (mean ±SE of relative expression; n = 10). Results represent one of three similar experiments;*P < 0.02 and **P < 0.000005. (Scale bar, 50 μm.) |
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| S8815New |
BSJ-03-123BSJ-03-123 是一种基于邻苯二甲酰亚胺的 cyclin-dependent kinase 6 (CDK6) 降解剂。(PROTAC) |
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| S7969New |
THZ2THZ2 是一种THZ1的类似物，是 CDK7 的选择性抑制剂，其IC50值为13.9 nM。THZ2 可有效抑制TNBC细胞的克隆形成生长，其IC50值约为10 nM。 |
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| S8903New |
AS2863619AS2863619 是一种小分子 cyclin-dependent kinase CDK8/19 抑制剂，其IC50分别为0.6099 nM和4.277 nM。AS2863619 在Tconv 细胞中可作为一种有效的 Foxp3 的诱导剂。 |
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| S8894New |
SR-4835SR-4835 是一种具有高度选择性的 CDK12 和 CDK13 的双重抑制剂，对CDK12的IC50值为99 nM，Kd值为98 nM，对CDK13的IC50值为4.9 nM。SR-4835 可抑制三阴性乳腺癌（TNBC）细胞的增殖。SR-4835 可促进与DNA损伤化学疗法和PARP抑制剂的协同作用。 |
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| S0500New |
Purvalanol BPurvalanol B (NG-95) 是一种有效的、选择性的 cyclin-dependent kinase (CDK) 的抑制剂，其对cdc2-cyclin B、CDK2-cyclin A、CDK2-cyclin E和CDK5-p35的IC50值分别为6 nM、6 nM、9 nM和6 nM。 |
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| S6777New |
NSC95397NSC 95397 是一种有效的、选择性 Cdc25 双特异性磷酸酶抑制剂，对于 Cdc25A、Cdc25B 和 Cdc25C 的Ki值分别为32 nM、96 nM 和 40 nM。NSC 95397 对 hCdc25A、hCdc25C 和 hCdc25B 的IC50值分别为22.3 nM、56.9 nM和125 nM。NSC 95397 抑制 mitogen-activated protein kinase phosphatase-1 (MKP-1) 和增殖，并通过 MKP-1 和 ERK1/2 途径诱导结肠癌细胞凋亡。 |
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| S2642New |
1-Naphthyl PP1(1-NA-PP1)1-Naphthyl PP1 (1-NA-PP 1)是一种高度选择性的、有效的 pan-PKD 抑制剂，对于PKD1、PKD2和PKD3的IC50值分别为154.6 nM、133.4 nM和109.4 nM。1-Naphthyl PP1是 Src family kinases (v-Src, c-Fyn) 和 the tyrosine kinase c-Abl 的选择性抑制剂， 对于v-Src、c-Fyn、c-Abl、CDK2和CAMK II的IC50值分别为1.0 μM、 0.6 μM、0.6 μM、18 μM 和 22 μM。 |
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| S1058New |
BI-1347BI-1347是Cyclin-dependent kinase 8(CDK8)的小分子抑制剂，IC50为1.1 nM。 |
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| S2009New |
Indirubin-3'-monoximeIndirubin-3'-monoxime是一种选择性的CDK抑制剂，对CDK1-cyclinB, CDK2-cyclinA, CDK2-cyclinE, CDK4-cyclinD1, CDK5-p35的IC50分别为 0.18 μM, 0.44 μM, 0.25 μM, 3.33 μM, 0.1 μM。Indirubin-3'-monoxime是一种直接、选择性的5-lipoxygenase抑制剂，IC50为7.8-10 µM。 |
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| S8730New |
BAY 1251152BAY1251152 is a potent PTEFb/CDK9 inhibitor with an IC50 value of 3 nM for CDK9 and an at least 50-fold selectivity against other CDKs in enzymatic assays. BAY1251152 binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing PTEFb-mediated activation of RNA Pol II and leading to the inhibition of gene transcription of various anti-apoptotic proteins. |
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| S8863New |
YKL-5-124YKL-5-124 is a potent, selective and covalent CDK7 inhibitor with an IC50 of 9.7 nM, 1300 nM and 3020 nM for inhibiting CDK7/Mat1/CycH, CDK2 and CDK9 respectively. It displays biochemical and cellular selectivity for CDK7 over CDK12/13. |
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| S6595New |
THZ531THZ531是CDK12和CDK13的选择性抑制剂，IC50值分别为158 nM和69 nM。 |
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| S6710New |
SGC-GAK-1SGC-GAK-1是一种有效的、具有细胞活性的cyclin G-associated kinase (GAK)抑制剂，Ki值为3.1 nM。对GAK的选择性比对其他相近激酶的选择性高50倍以上。 |
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| S6727New |
AX-024 HClAX-024可抑制CD3ε PRS与SH3.1(Nck)的相互作用。 |
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| S8809New |
MC180295MC180295是一种新型有效的选择性CDK9抑制剂，IC50为5 nM，对CDK9的选择性比对其他CDKs高至少22倍。 |
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| S6531New |
BohemineBohemine是CDK抑制剂，对Cdk2/cyclin E, Cdk2/cyclin A和Cdk9/cyclin T1的IC50值分别为4.6, 83和2.7 μM。 |
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| S6540New |
NG 52NG-52是三取代嘌呤，可结合酵母CDK的ATP结合区域，抑制Cdc28p和Pho85p，IC50分别为7 μM和2 μM。 |
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| S8722New |
ICEC0942 (CT7001)ICEC0942 (CT7001)是一种新型口服的CDK7抑制剂，IC50为40 nM。它对其他CDK蛋白，如CDK1、CDK2、CDK5和CDK9的IC50值别为是对CDK7的IC50的45、15、230和30倍。 |
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| S6537New |
CVT-313CVT-313是有效的CDK2抑制剂，在体外的IC50值为0.5 μM。它对其他非相关的、依赖于ATP的丝氨酸/苏氨酸激酶没有作用。 |
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| S8568New |
G1T38Lerociclib (G1T38)是一种新型有效的、具有口服活性的CDK4/6抑制剂，对CDK4、CDK6和CDK9的IC50值分别为0.001 μM、0.002 μM和0.028 μM。 |
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| S1524 |
AT7519AT7519 是多种CDK抑制剂，作用于CDK1， 2， 4， 6和9时，IC50为10-210 nM，对CDK3作用效果稍弱，对CDK7几乎没有抑制活性。AT7519 也可抑制GSK3β对应的IC50值为89 nM。AT7519 可诱导凋亡。Phase 2。 |
Lysates of MDM treated with five-fold dilutions of the indicated compounds (starting concentration: AT7519, 0.5 mmol/l, roscovitine 4 mmol/l) were subjected to SDS-PAGE, transferred, and immunoblotted with antiphopho-SAMHD1, anti-SAMHD1 and anti-Hsp90 antibodies. MDM, monocyte-derived macrophage; SAMHD1, sterile a motif and HD domain-containing protein-1; SD, standard deviation.
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| S2679 |
Flavopiridol HClFlavopiridol HCl与ATP竞争性抑制CDKs，作用于CDK1，CDK2，CDK4和CDK6，无细胞试验中IC50为~40 nM。作用于CDK1/2/4/6比作用于CDK7选择性高7.5倍。Flavopiridol最初被发现可抑制EGFR和PKA。Phase 1/2。 |
Comparative efficacy of anticancer therapies (Flavopiridol, vincristine, daunorubicin, et al.) in NMC vs non-NMC cell lines. Mean IC50 (± s.e.m.) of the indicated agents in three NMC (PER-403, PER-624, and PER-704) and two non-NMC cell lines (PER-535 and SAOS2), ***P<0.001, unpaired t-test, corrected for multiple testing. |
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| S1249 |
JNJ-7706621JNJ-7706621是一种泛CDK抑制剂，对CDK1/2抑制作用最强，无细胞试验中IC50为9 nM/4 nM，作用于CDK1/2比作用于CDK3/4/6选择性高6倍以上。也能有效抑制Aurora A/B，对Plk1和Wee1没有抑制活性。 |
JNJ-7706621 treatment of tamoxifen-resistant cell lines leads to arrest in the G2 cell cycle phase. M phase cells from the upper right quadrants were quantified relative to total G2/M phase cells. Statistical significant differences from vehicle-treated cells are denoted by asterisks; *P<0.05, **P<0.01.
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| S2672 |
PF-00562271 BesylatePF-00562271 Besylate是PF-562271的苯磺酸盐，是一种有效的，ATP竞争性，可逆的FAK抑制剂，IC50为1.5 nM，作用于Pyk2比作用于FAK效果低10倍左右，比作用于其他蛋白激酶（除了一些CDKs）选择性高100倍以上。Phase 1。 |
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| S2621 |
AZD5438AZD5438是一种有效的CDK1/2/9抑制剂，无细胞试验中IC50为16 nM/6 nM/20 nM。对CDK5/6作用效果稍弱，对GSK3β也有抑制作用。Phase 1。 |
(a) HEK-293 cells expressing V5-EXO1 were synchronized in different phases of the cell cycle. EXO1 was immunoprecipitated (IP) with anti-V5 antibody and Western blotted with anti-phospho-Ser (p-SP) or anti-phospho-Thr (p-TP) CDK substrate antibodies, as indicated. “+AZD” indicates cells pre-treated with the CDK inhibitor AZD5438 prior to analysis. (b) HEK-293 cells expressing V5-EXO1, synchronized in G2, were pre-treated with CDK inhibitors, AZD5438 or Roscovitine, prior to analysis of EXO1 phosphorylation by IP-Western.
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| S2735 |
MK-8776 (SCH 900776)MK-8776 (SCH 900776)是一种选择性Chk1抑制剂，无细胞试验中IC50为3 nM，比作用于Chk2选择性高500倍。Phase 2。 |
Hela cell was trypsinized and plated at 30% confluence in DMEM. 16 hours later, MK-8776 (SCH900776) was added at final concentrations of 0, 5, 10 and 25uM. Another 24 hours later, cells were harvested in RIPA with protease and phosphatase inhibitor cocktail. Total protein concentration was measured by BCA method. Lysates equivalent to 20ug total protein were subject to Western Blot, using total- CHK1, pS345-CHK1 and beta-actin (internal control) antibodies. |
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| S2890 |
PF-562271PF-562271是一种有效的，ATP竞争性的，可逆的FAK抑制剂，无细胞试验中IC50为1.5 nM，作用于FAK比作用于Pyk2选择性高10倍左右，比作用于其他蛋白激酶（除了一些CDKs）选择性高100倍以上。 |
VEGF and P450 enzyme production in response to FAK or Src inhibitors. MCF10A cells were cultured in LD collagen gels ?vehicle control (V), 10 uM PF-562271 FAK ATP inhibitor (PF) or Src inhibitor PP2 for 24 h. Cells were also lysed and examined for CYP1A1 or CYP4B1 by immunoblot (B and C) and densitometry (D and E). VEGF data are displayed as the mean normalized to the vehicle control, N = 6, 盨EM, *p < 0.003 vs control (A). P450 data are displayed as the mean relative to GAPDH and normalized to the control. N > 4, ±SEM, *p < 0.05 vs respective control (D and E). |
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| S1487 |
PHA-793887PHA-793887是一种新型有效的CDK2，CDK5和CDK7抑制剂，IC50分别为8 nM， 5 nM 和10 nM，作用于CDK2， 5，和7比作用于CDK1， 4，和9选择性高6倍以上。Phase 1。 |
J558 cells were treated with PHA793887 (0.02–5 umol/L) for 6 hours, after which Western blot analysis was performed to monitor XBP-1s expression. Tub, tubulin.
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| S1572 |
BS-181 HClBS-181 HCl是一种高度选择性的CDK7抑制剂，IC50为21 nM，作用于CDK7比作用于CDK1， 2， 4， 5， 6，和9选择性高40倍以上。 |
Dose-response inhibition of purified human recombinant cyclin-dependent kinase CDK7/cyclin H by inhibitor BS-181 (left panel). Immunoblotting of RNA polymerase II and its phosphorylated form (at Ser5), physiological substrate of CDK7, in MCF-7 cells treated with different doses of inhibitor BS-181 for 24 h (right panel). |
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| S1579 |
Palbociclib (PD0332991) IsethionatePalbociclib (PD0332991) Isethionate是一种高度选择性的CDK4/6抑制剂，无细胞试验中IC50为11 nM/16 nM，对CDK1/2/5，EGFR，FGFR，PDGFR， InsR等没有抑制活性。Phase 3。 |
HT29 cells were treated with DMSO control, 1 uM selumetinib (Sel) or 5 uM PD0332991 (991) for 24 or 48 h after which time cells were lysed, subjected to SDS/PAGE and immunoblotted with the indicated antibodies.
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| S2670 |
A-674563A-674563是一种Akt抑制剂，在无细胞试验中Ki为11 nM，对PKA适度有效，作用于Akt1比作用于PKC选择性高30多倍。 |
B cells were pre-treated with the indicated concentrations of A-674563 for 1h prior to R848 treatment (500 ng/ml). Thymidine incorporation was analyzed 24h later. |
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| S7158 |
abemaciclib mesylate (LY2835219)abemaciclib (LY2835219)是一种有效的，选择性CDK4和CDK6抑制剂，无细胞试验中IC50分别为2 nM和10 nM。Phase 3。 |
HT29 cells were treated with DMSO control, 1 uM selumetinib (Sel), 5 uM PD0332991 (991), 0.3 uM LY2835219 (219) or serum-free (SF) medium for 48 h. Whole cell extracts were prepared, fractionated by SDS/PAGE and analysed by Western blotting with the indicated antibodies. |
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| S2014 |
BMS-265246BMS-265246是一种有效的选择性CDK1/2抑制剂，无细胞试验中IC50为6 nM/9 nM。作用于CDK1/2 比作用于CDK4选择性高25倍。 |
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| S2742 |
PHA-767491PHA-767491是一种有效的，ATP竞争性的，双重Cdc7/CDK9抑制剂，无细胞试验中IC50分别为10 nM和34 nM，比作用于CDK1/2和GSK3-β选择性高20倍左右，比作用于MK2和CDK5选择性高50倍，比作用于PLK1和CHK2选择性高100倍。 |
Viability at 250 nM and CI vs. Fa for U2932 following 24 hours exposure to ABT-199, additional drugs with activity against CDK9, or the combinations. Mean of quadruplicates ± SEM. |
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| S2751 |
Milciclib (PHA-848125)Milciclib (PHA-848125)是一种有效的，ATP竞争性CDK抑制剂，作用于CDK2，IC50为45 nM，作用于CDK2比作用于CDK1， 2， 4， 5和7选择性高3倍以上。 Milciclib (PHA-848125)可通过自噬来诱导细胞死亡。Phase 2。 |
Cell survival curves of A549 cells treated with increasing doses of A-674563, PHA-848125, and H89 2HCl for 72 hours. Cells were incubated with cell proliferation reagent WST-1 for 2 hours and absorbance was read at 450nm. Optical density was then normalized to a 1% DMSO control. The data is presented as the percentage of cell survival relative to the DMSO control ± SEM of three independent trials. Statistical significance was determined with multiple T-tests using the Holm-Sidak method without assuming a consistent SD and is represented by *p<0.05.
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| S2688 |
R547R547是一种有效的，ATP竞争性CDK1/2/4抑制剂，Ki为2 nM/3 nM/1 nM，对CDK7和GSK3α/β作用效果稍弱，而抑制其他激酶活性。Phase 1。 |
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| S7440 |
Ribociclib (LEE011)Ribociclib (LEE011)是一种口服具有活性的，高度特异性CDK4/6抑制剂。Phase 3。 |
Analysis of apoptosis in leukemia cells induced by LEE011. Annexin V staining of cells following 48-h treatment with LEE011 at 2 or 5 µM compared with DMSO controls. Following 5-µM LEE011 treatment, the K562 apoptotic cell percentage was 5.9 ± 0.75 vs. 1.2 ± 0.66% for the DMSO group, P = 0.001; in MV4-11 cells, the apoptotic cell percentage was 24.2 ± 3.06 vs. 0.53 ± 0.40% for the DMSO group, P = 0.005; in U937 cells, the apoptotic cell percentage was 9.9 ± 2.81 vs. 0.57 ± 0.42% for the DMSO group, P = 0.027; in HL-60 cells, the apoptotic cell percentage was 28.23 ± 6.01 vs. 0.9 ± 0.8% for the DMSO group, P = 0.015; in THP-1 cells, the apoptotic cell percentage was 1.76 ± 0.4 vs. 1.56 ± 0.45% for the DMSO group, P = 0.59; in CCRF cells, the apoptotic cell percentage was 13.77 ± 3.16 vs. 1.2 ± 0.36% for the DMSO group, P = 0.019; in NB4 cells, the apoptotic cell percentage was 12.1 ± 1.35 vs. 0.86 ± 0.25% for the DMSO group, P = 0.004; and in SHI-1 cells the apoptotic cell percentage was 12.6 ± 2.81 vs. 1.87 ± 0.75% for the DMSO group, P = 0.017. These analyses were repeated three times. *P < 0.05; **P < 0.01 |
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| S7114 |
NU6027NU6027是一种有效的ATR/CDK抑制剂，抑制CDK1/2， ATR和DNA-PK时，Ki分别为2.5 μM/1.3 μM， 0.4 μM和 2.2 μM ，进入细胞时比6-氨基嘌呤类抑制剂更容易。 |
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| S7357 |
PF-562271 HClPF-562271 HCl是PF-562271的盐酸盐形式，是一种强效的ATP竞争性的可逆的抑制剂，作用于FAK其IC50为1.5 nM。相比较FAK，对Pyk2的效果少了大约十倍，除了CDKs类的蛋白酶，PF-562271 HCl的选择性相比其他蛋白酶大大约100倍。 |
VEGF and P450 enzyme production in response to FAK or Src inhibitors. MCF10A cells were cultured in LD collagen gels ?vehicle control (V), 10 uM PF-562271 FAK ATP inhibitor (PF) or Src inhibitor PP2 for 24 h. Cells were also lysed and examined for CYP1A1 or CYP4B1 by immunoblot (B and C) and densitometry (D and E). VEGF data are displayed as the mean normalized to the vehicle control, N = 6, 盨EM, *p < 0.003 vs control (A). P450 data are displayed as the mean relative to GAPDH and normalized to the control. N > 4, ±SEM, *p < 0.05 vs respective control (D and E). |
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| S8058 |
Riviciclib hydrochloride (P276-00)Riviciclib hydrochloride (P276-00) 是一种新型的CDK1，CDK4和CDK9抑制剂，IC50分别为79 nM， 63 nM和20 nM。Phase 2/3。 |
Predicted anticancer drugs inhibit the growth of neuroendocrine tumor cells. Multi-tyrosine kinase inhibitors sorafenib, sunitinib, regorafenib and cabozantinib effectively inhibit GOT1 cell growth with IC50 values in the micromolar range. Inhibitors of AKT (MK-2206), HDAC (vorinostat), HSP90 (alvespimycin) and CDK4/9 (P276-00) also inhibited GOT1 cell growth at micromolar concentrations, whereas inhibition of PARP1 (veliparib) had no effect. GOT1 cells were treated with anticancer drugs at various concentrations for 4 days. Cell viability was estimated using AlamarBlue®. Data points are the mean values of three individual experiments carried out in triplicate (n=9). Fitting of curves was done in GraphPad Prism software v6.04 using log (inhibitor) vs response nonlinear fit with variable slope. IC50 was interpolated at Y=50 and bars denote ±s.d. |
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| S8727 |
Atuveciclib (BAY-1143572)Atuveciclib (BAY-1143572)是一种有效的、高选择性PTEFb/CDK9抑制剂，对CDK9/CycT的IC50值为13 nM。它对CDK2的IC50是其对CDK9的约100倍。除了CDK家族成员，它还抑制GSK3激酶，对GSK3α和GSK3β的IC50值分别为45 nM和87 nM。 |
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| S7549 |
THZ1 2HClTHZ1是共价的CDK7抑制剂，对位于经典的激酶结构域外端的半胱氨酸残基具有结合能力，对CDK7选择性高。 |
One and three days after differentiation induction, protein level of Myh3 and Myogenin were analyzed by western blot.
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| S7320 |
TG003TG003是一种强效的ATP竞争性的Cdc2-like激酶(Clk)抑制剂，作用于Clk1, Clk2,和Clk4时IC50分别为20 nM, 200 nM,和15 nM。对Clk3, SRPK1, SRPK2, 或者PKC无抑制效果。 |
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| S5316 |
NU2058NU2058 is an inhibitor of CDK2 with IC50 value of 17 μM in an isolated enzyme assay. It also potentiates melphalan (DMF 2.3), and monohydroxymelphalan (1.7), but not temozolomide or ionising radiation. |
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| S7747 |
Ro-3306RO-3306是一种ATP竞争性的选择性 CDK1 抑制剂，Ki 为20 nM，选择性是其他各种人类激酶的15倍多。RO-3306可增强p53介导的 Bax 激活和线粒体的凋亡。 |
HeLa cells were untreated or treated with either colcemid (10 μg/ml for 16 h), RO-3306 (9 μM for 16 h), or both colcemid and RO-3306, as indicated. Cells were then lysed, and proteins were detected by Western analysis.
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| S7992 |
LDC4297 (LDC044297)LDC4297是一种新型的CDK7抑制剂，抑制CDK7的IC50为0.13±0.06 nM，对其他CDKs的IC50范围为10-10,000 nM。 |
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| S8520 |
Senexin ASenexin A是有效的、选择性的CDK8抑制剂，还抑制CDK19，Kd值分别为0.83 μM和0.31 μM。 |
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| S8387 |
MSC2530818MSC2530818是一种CDK8抑制剂，IC50为2.6 nM。具有良好的激酶选择性、生化和细胞效力、微粒体稳定性，并具有生物口服活性。 |
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| S4743 |
WogoninWogonin，在植物中发现的天然活性黄酮类化合物，是CDK9的抑制剂。在抑制CDK9的浓度下，对CDK2、CDK4和CDK6没有抑制作用。也可抑制N-acetyltransferase。 |
Effect of Wogonin on the translocation and transcriptional activity of NFATc1. U2OS cells stably transfected with EGFP-NFATc1, RANKL (100 ng/ml) and different concentrations of Wogonin (5.0, 1.0, 0.1 and 0.0 mM) were added and incubated for 24 h. The IN Cell™ Analyzer 1000 was used to observe the translocation of NFATc1. (A) DMSO was used as a control. RANKL (100 ng/ml) significantly stimulated the translocation of NFATc1; Wogonin (5 mM) significantly decreased the translocation of NFATc1 induced by RANKL (magnification, x200). (B) Statistics showed that Wogonin could decrease the translocation of NFATc1 into the nucleus induced by RANKL in a concentration-dependent manner. RAW264.7 cells were transfected with pGL3-promoter-NFATc1-RE, and then RANKL (100 ng/ml) and different concentrations of Wogonin (5.0, 1.0, 0.1 and 0.0 mM) were added and incubated for 24 h. (C) RANKL significantly increased the transcriptional activity of NFATc1 and Wogonin decreased the transcriptional activity of NFATc1 induced by RANKL in a concentration-dependent manner. n=3; *P<0.05 and ***P<0.001 compared with the RANKL group. NAFTc1, nuclear factor of activated T cells c1; EGFP, enhanced green fluorescent protein; DMSO, dimethylsulfoxide, RANKL, receptor activator of nuclear factor κB ligand; RE, response element.
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| S7793 |
Purvalanol APurvalanol A 是一种有效的，细胞渗透性 CDK 抑制剂，对cdc2-cyclin B，cdk2-cyclin A，cdk2-cyclin E，和 cdk4-cyclin D1的 IC50 分别为 4 nM，70 nM，35 nM，和 850 nM。 |
After 12 h PAB treatment, cells were treated with PAB in the absence and presence of RO-3306 or purvalanol A for 12 h and 36 h. (A) Expressions of p-histone h3 were detected by western blot.
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| S7511 |
LY2857785LY2857785是一种I型可逆的、ATP竞争性的CDK9抑制剂(IC50=0.011 μM)，还可抑制其他转录激酶如CDK8(IC50=0.016 μM)和CDK7 (IC50=0.246 μM)。 |
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| S8100 |
K03861K03861是II型 CDK2 抑制剂，作用于CDK2(WT)，CDK2(C118L)，CDK2(A144C)，和 CDK2(C118L/A144C)的 Kd 分别为 50 nM，18.6 nM，15.4 nM，和 9.7 nM。 |
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| S7509 |
ML167ML167 是一种高度选择性Cdc2-like kinase 4 (Clk4)抑制剂，IC50为136 nM, 其选择性高于相近的激酶Clk1-3和Dyrk1A/1B 10倍。 |
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| S7917 |
KenpaulloneKenpaullone是CDKs的ATP竞争性抑制剂， 它同样也抑制GSK3β，IC50为0.23 μM。 |
Effect of Kenpaullone on GSK-3β and CDKs. (A and B) Naïve CD4+ T cells were stimulated with anti-CD3/CD28 (TCR), TGF-β (5 ng/ml) and IL-6 (20 ng/ml) in the presence of the indicated Kenpaullone (Kenp) concentrations for 30 min (A) or 24 h (A and B).
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| S8652 |
Skp2 inhibitor C1 (SKPin C1)Skp2 inhibitor C1 (SKPin C1)是一种高选择性的Skp2-mediated p27 degradation小分子抑制剂。 |
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| S8161 |
ON123300ON123300是有效的多靶点激酶抑制剂，对CDK4, Ark5, PDGFRβ, FGFR1, RET, Fyn的IC50分别为3.9 nM, 5 nM, 26 nM, 26 nM, 9.2 nM和11nM。 |
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| S5716 |
AbemaciclibAbemaciclib is a cell cycle inhibitor selective for CDK4/6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively. |
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| S7461 |
LDC000067LDC000067 是高度选择性CDK9抑制剂，IC50为44 nM,比作用于CDK2/1/4/6/7的选择性分别高55/125/210/ >227/ >227倍。 |
Inhibition of CDK9 leads to a decrease in RNApol II activity and repetitive element expression. HEK293T cells were treated with DMSO control and the indicated amounts of LDC000067, a CDK9 inhibitor, for a total of 3 h. (A) Immunoblots showing the levels of phosphorylated RNApol II largest subunit (pRPB1), total RPB1 and GAPDH, in response to different doses of CDK9 inhibitor. (B) Quantification of immunoblots from 2 independent experiments in which each condition was performed in duplicates, and in which pRPB1 and total RPB1 protein levels were normalized to GAPDH or as pRPB1/Total RPB1 ratio. (C, D) qRT-PCR analyses show a significant response to CDK9 inhibition of repetitive elements belonging to the LTR (C) and SINE (D) classes. Statistical analyses were performed to compare all groups using a One-way ANOVA followed by Bonforreoni’s multiple comparison test, *P < 0.05, **P < 0.01, #P < 0.0001. |
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| S7636 |
SU9516SU9516是一种3位取代的吲哚酮类CDK抑制剂，对CDK2，CDK1，和CDK4的IC50分别为22 nM，40 nM，和200 nM。 |
a, Porcine blastocysts derived from the SU9516-treated group. Scale bar 100 μM. b, An image of a 7 day SU9516- treated parthenogenetically activated porcine embryo stained with Hoechst 33342. Scale bar 100 μM. c, Tetraploid karyotype from SU9516 treated blastocysts. Scale bar 50 μM. d, Porcine blastocysts derived from the cytochalasin B (CB)-treated group. Scale bar 100 μM. e, An image of a 7 day CB-treated parthenogenetically activated porcine embryo stained with Hoechst 33342. Scale bar 100 μM. f, diploid karyotype from CB treated blastocysts. Scale bar 50 μM
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| S7808 |
AT7519 HClAT7519 HCl是一种多重CDK抑制剂，作用于CDK1，2，4，6 和 9，无细胞试验中IC50为10-210 nM。它对CDK3作用较弱，而对CDK7几乎没有活性。Phase 2。 |
(c) Effect of AT7519 treatment on RNA pol II occupancy at the PRCC gene. MM1.S cells were treated with either DMSO vehicle (blue) or 2 μM AT7519 (brown) for 6 h, followed by RNA pol II ChIP-seq analysis. Twenty-fold magnifications of the rpm/bp scale of these gene tracks are shown in the right panel to show the difference in reads for elongating RNA pol II. TR, RNA pol II traveling ratio.
(d) Genome-wide binding average RNA pol II (ChIP-seq) on active promoters and gene bodies following treatment of MM1.S cells with DMSO vehicle (blue) or 2 μM of AT7519 (brown) for 6 h. Magnification of the rpm/bp scale at gene bodies is shown in the inset. The inset includes RNA polymerase II traveling ratio distributions (TR, mean) derived from MM1.S cells treated with DMSO (blue) or 2 μM AT7519 (red).
(e) Chemical structures of the pan-CDK inhibitor AT7519 and its biotinylated counterpart bio-AT7519.
(f) In vitro kinase assays with recombinant cyclin T-CDK9 complex in the presence of increasing concentrations of AT7519 or bio-AT7519. The derived IC50 values for each compound are shown.
(g) Effect of AT7519 and bio-AT7519 on MM1.S cell proliferation. Cells were treated with varying concentrations of drug for 72 h as indicated. The derived EC50 values for each compound are shown.
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| S8719 |
AZD4573AZD4573是有效的CDK9抑制剂（IC50<0.004 μM），具有高选择性。 |
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| S7547 |
XL413 (BMS-863233)XL413 (BMS-863233) 是强效的选择性的cell division cycle 7 homolog (CDC7) kinase抑制剂，IC50为3.4 nM,其选择性分别超过 CK2, Pim-1 和pMCM2选择性的 63-, 12-和35-倍。 Phase 1/2。 |
The protein levels of p-MCM2 and p-ERK in NOK, HN6 and Cal27 cells treated with 0, 10 and 20 μMXL413 were detected by western blotting.
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| S8840 |
SEL120(SEL120-34A) hydrochlorideSEL120(SEL120-34,SEL120-34A)是一种新型的CDK8抑制剂，对CDK8和CDK19的IC50值分别为4.4 nM和10.4 nM。 |
| 目录号 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S1116 |
Palbociclib (PD-0332991) HClPalbociclib (PD-0332991) HCl是一种高度选择性的CDK4/6抑制剂，无细胞试验中IC50分别为11 nM/16 nM。它对CDK1/2/5，EGFR，FGFR，PDGFR，InsR等没有抑制活性。Phase 3。 |
Patient tumor cell sensitivity to combinatorial treatment with histone deacetylase (HDAC)/cyclin-dependent kinase (CDK) inhibitors in 3-D culture. The effect of each drug or drug combination was assessed by fluorescent dye to identify live (green) and dead cells (red). Cells from breast reduction patients were used as non-cancer control in the assay. |
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| S1153 |
Roscovitine (Seliciclib,CYC202)Roscovitine (Seliciclib,CYC202)是一种有效的，选择性CDK抑制剂，作用于Cdc2，CDK2和CDK5时，无细胞试验中IC50分别为0.65 μM，0.7 μM和0.16 μM，对CDK4/6几乎没有作用。Phase 2。 |
Inhibition of CDK5 by roscovitine resulted in defective neuronal migration, which was rescued by expression of GFP-Ndel1 (S251E). a, Granular neurons were treated with roscovitine. Western blotting was performed 24 h after start of culture. Aurora-A and NDEL1 displayed similar expression levels with untreated neurons, whereas the levels of phosphorylated Aurora-A and NDEL1 proteins were decreased after treatment with roscovitine. Relative intensities of the bands of Western blotting are shown at the bottom. |
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| S1145 |
SNS-032 (BMS-387032)SNS-032 (BMS-387032)最初被描述为选择性CDK2抑制剂，无细胞试验中IC50为48 nM，比作用于CDK1/CDK4选择性高10和20倍。它也对CDK7/9敏感，IC50为62 nM/4 nM，对CDK6几乎没有抑制效果。 Phase 1。 |
HeLa cells were treated for 3h with PIK-75 or SNS-032 at the indicated concentrations. Cells were subsequently lysed and subjected to western blotting. One representative of two independent experiments is shown.
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| S2768 |
Dinaciclib (SCH727965)Dinaciclib (SCH727965)是一种新型有效的CDK抑制剂，作用于CDK2，CDK5，CDK1和CDK9，无细胞试验中IC50分别为1 nM，1 nM，3 nM和4 nM。它也会阻断胸甘(dThd) DNA整合。Dinaciclib 可通过激活caspases 8和caspases 9来诱导细胞凋亡。Phase 3。 |
CDK4/6 inhibition has potent cytostatic effect in HER2-positive models. The indicated cells were treated with PD-0332991 (1 uM) or Dinaciclib (1 uM) for 96 hours and plates were stained with crystal violet.
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| S1230 |
Flavopiridol (Alvocidib)Flavopiridol (Alvocidib) 与ATP竞争性抑制CDKs，包括CDK1、CDK2、CDK4、CDK6和CDK9的IC50范围为20-100 nM。作用于CDK1、2、4、6、9比作用于CDK7更具有选择性。Flavopiridol最初被发现能抑制EGFR和PKA。Flavopiridol可诱导自噬和内质网应激反应。Flavopiridol可阻滞HIV-1的复制。Phase 1/2。 |
(C) In vivo treatment of Tg:Pomc-Pttg;Pomc-eGFP embryos with small-molecule CDK inhibitors (50 μM) or 0.2% DMSO as control from 18 to 40 hpf. One hundred to one hundred fifty embryos were treated with each compound. Representative images of live embryos are shown with gross morphology (Right) and pituitary Pomc-GFP-positive cells at higher magnification (Left) at 40 hpf. Embryos exposed to flavopiridol developed early developmental defect before pituitary POMC cell ontogeny occurs. (D) Relative expression of pituitary Pomc-eGFP fluorescence analyzed using Volocity 5.2 software (Improvision; mean ±SE of relative expression, n = 7). (E) R-roscovitine specifically suppresses expansion of pituitary POMC cells overexpressing zPttg from 18 to 48 hpf. Double transgenic Tg:Pomc-Pttg;Prl-RFP embryos were generated by breeding Tg:Pomc-Pttg fish with a previously generated PRL-RFP transgenic line, in which RFP was targeted to pituitary lactotrophs by a zebrafish Prolactin promoter (34). Representative fluorescent microscopy of pituitary POMC-eGFP (a and b) and PRL-RFP (c and d) expression in live Tg:Pomc-Pttg; Pomc-eGFP and Tg:Pomc-Pttg;Prl-RFP embryos treated with 0.2% DMSO (a and c) or 50 μM R-roscovitine (b and d). (F) Relative expression of pituitary POMC-eGFP or PRL-RFP fluorescence were analyzed (mean ±SE of relative expression; n = 10). Results represent one of three similar experiments;*P < 0.02 and **P < 0.000005. (Scale bar, 50 μm.) |
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| S8815New |
BSJ-03-123BSJ-03-123 是一种基于邻苯二甲酰亚胺的 cyclin-dependent kinase 6 (CDK6) 降解剂。(PROTAC) |
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| S7969New |
THZ2THZ2 是一种THZ1的类似物，是 CDK7 的选择性抑制剂，其IC50值为13.9 nM。THZ2 可有效抑制TNBC细胞的克隆形成生长，其IC50值约为10 nM。 |
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| S8903New |
AS2863619AS2863619 是一种小分子 cyclin-dependent kinase CDK8/19 抑制剂，其IC50分别为0.6099 nM和4.277 nM。AS2863619 在Tconv 细胞中可作为一种有效的 Foxp3 的诱导剂。 |
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| S8894New |
SR-4835SR-4835 是一种具有高度选择性的 CDK12 和 CDK13 的双重抑制剂，对CDK12的IC50值为99 nM，Kd值为98 nM，对CDK13的IC50值为4.9 nM。SR-4835 可抑制三阴性乳腺癌（TNBC）细胞的增殖。SR-4835 可促进与DNA损伤化学疗法和PARP抑制剂的协同作用。 |
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| S0500New |
Purvalanol BPurvalanol B (NG-95) 是一种有效的、选择性的 cyclin-dependent kinase (CDK) 的抑制剂，其对cdc2-cyclin B、CDK2-cyclin A、CDK2-cyclin E和CDK5-p35的IC50值分别为6 nM、6 nM、9 nM和6 nM。 |
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| S6777New |
NSC95397NSC 95397 是一种有效的、选择性 Cdc25 双特异性磷酸酶抑制剂，对于 Cdc25A、Cdc25B 和 Cdc25C 的Ki值分别为32 nM、96 nM 和 40 nM。NSC 95397 对 hCdc25A、hCdc25C 和 hCdc25B 的IC50值分别为22.3 nM、56.9 nM和125 nM。NSC 95397 抑制 mitogen-activated protein kinase phosphatase-1 (MKP-1) 和增殖，并通过 MKP-1 和 ERK1/2 途径诱导结肠癌细胞凋亡。 |
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| S2642New |
1-Naphthyl PP1(1-NA-PP1)1-Naphthyl PP1 (1-NA-PP 1)是一种高度选择性的、有效的 pan-PKD 抑制剂，对于PKD1、PKD2和PKD3的IC50值分别为154.6 nM、133.4 nM和109.4 nM。1-Naphthyl PP1是 Src family kinases (v-Src, c-Fyn) 和 the tyrosine kinase c-Abl 的选择性抑制剂， 对于v-Src、c-Fyn、c-Abl、CDK2和CAMK II的IC50值分别为1.0 μM、 0.6 μM、0.6 μM、18 μM 和 22 μM。 |
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| S1058New |
BI-1347BI-1347是Cyclin-dependent kinase 8(CDK8)的小分子抑制剂，IC50为1.1 nM。 |
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| S2009New |
Indirubin-3'-monoximeIndirubin-3'-monoxime是一种选择性的CDK抑制剂，对CDK1-cyclinB, CDK2-cyclinA, CDK2-cyclinE, CDK4-cyclinD1, CDK5-p35的IC50分别为 0.18 μM, 0.44 μM, 0.25 μM, 3.33 μM, 0.1 μM。Indirubin-3'-monoxime是一种直接、选择性的5-lipoxygenase抑制剂，IC50为7.8-10 µM。 |
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| S8730New |
BAY 1251152BAY1251152 is a potent PTEFb/CDK9 inhibitor with an IC50 value of 3 nM for CDK9 and an at least 50-fold selectivity against other CDKs in enzymatic assays. BAY1251152 binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing PTEFb-mediated activation of RNA Pol II and leading to the inhibition of gene transcription of various anti-apoptotic proteins. |
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| S8863New |
YKL-5-124YKL-5-124 is a potent, selective and covalent CDK7 inhibitor with an IC50 of 9.7 nM, 1300 nM and 3020 nM for inhibiting CDK7/Mat1/CycH, CDK2 and CDK9 respectively. It displays biochemical and cellular selectivity for CDK7 over CDK12/13. |
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| S6595New |
THZ531THZ531是CDK12和CDK13的选择性抑制剂，IC50值分别为158 nM和69 nM。 |
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| S6710New |
SGC-GAK-1SGC-GAK-1是一种有效的、具有细胞活性的cyclin G-associated kinase (GAK)抑制剂，Ki值为3.1 nM。对GAK的选择性比对其他相近激酶的选择性高50倍以上。 |
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| S6727New |
AX-024 HClAX-024可抑制CD3ε PRS与SH3.1(Nck)的相互作用。 |
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| S8809New |
MC180295MC180295是一种新型有效的选择性CDK9抑制剂，IC50为5 nM，对CDK9的选择性比对其他CDKs高至少22倍。 |
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| S6531New |
BohemineBohemine是CDK抑制剂，对Cdk2/cyclin E, Cdk2/cyclin A和Cdk9/cyclin T1的IC50值分别为4.6, 83和2.7 μM。 |
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| S6540New |
NG 52NG-52是三取代嘌呤，可结合酵母CDK的ATP结合区域，抑制Cdc28p和Pho85p，IC50分别为7 μM和2 μM。 |
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| S8722New |
ICEC0942 (CT7001)ICEC0942 (CT7001)是一种新型口服的CDK7抑制剂，IC50为40 nM。它对其他CDK蛋白，如CDK1、CDK2、CDK5和CDK9的IC50值别为是对CDK7的IC50的45、15、230和30倍。 |
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| S6537New |
CVT-313CVT-313是有效的CDK2抑制剂，在体外的IC50值为0.5 μM。它对其他非相关的、依赖于ATP的丝氨酸/苏氨酸激酶没有作用。 |
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| S8568New |
G1T38Lerociclib (G1T38)是一种新型有效的、具有口服活性的CDK4/6抑制剂，对CDK4、CDK6和CDK9的IC50值分别为0.001 μM、0.002 μM和0.028 μM。 |
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| S1524 |
AT7519AT7519 是多种CDK抑制剂，作用于CDK1， 2， 4， 6和9时，IC50为10-210 nM，对CDK3作用效果稍弱，对CDK7几乎没有抑制活性。AT7519 也可抑制GSK3β对应的IC50值为89 nM。AT7519 可诱导凋亡。Phase 2。 |
Lysates of MDM treated with five-fold dilutions of the indicated compounds (starting concentration: AT7519, 0.5 mmol/l, roscovitine 4 mmol/l) were subjected to SDS-PAGE, transferred, and immunoblotted with antiphopho-SAMHD1, anti-SAMHD1 and anti-Hsp90 antibodies. MDM, monocyte-derived macrophage; SAMHD1, sterile a motif and HD domain-containing protein-1; SD, standard deviation.
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| S2679 |
Flavopiridol HClFlavopiridol HCl与ATP竞争性抑制CDKs，作用于CDK1，CDK2，CDK4和CDK6，无细胞试验中IC50为~40 nM。作用于CDK1/2/4/6比作用于CDK7选择性高7.5倍。Flavopiridol最初被发现可抑制EGFR和PKA。Phase 1/2。 |
Comparative efficacy of anticancer therapies (Flavopiridol, vincristine, daunorubicin, et al.) in NMC vs non-NMC cell lines. Mean IC50 (± s.e.m.) of the indicated agents in three NMC (PER-403, PER-624, and PER-704) and two non-NMC cell lines (PER-535 and SAOS2), ***P<0.001, unpaired t-test, corrected for multiple testing. |
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| S1249 |
JNJ-7706621JNJ-7706621是一种泛CDK抑制剂，对CDK1/2抑制作用最强，无细胞试验中IC50为9 nM/4 nM，作用于CDK1/2比作用于CDK3/4/6选择性高6倍以上。也能有效抑制Aurora A/B，对Plk1和Wee1没有抑制活性。 |
JNJ-7706621 treatment of tamoxifen-resistant cell lines leads to arrest in the G2 cell cycle phase. M phase cells from the upper right quadrants were quantified relative to total G2/M phase cells. Statistical significant differences from vehicle-treated cells are denoted by asterisks; *P<0.05, **P<0.01.
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| S2672 |
PF-00562271 BesylatePF-00562271 Besylate是PF-562271的苯磺酸盐，是一种有效的，ATP竞争性，可逆的FAK抑制剂，IC50为1.5 nM，作用于Pyk2比作用于FAK效果低10倍左右，比作用于其他蛋白激酶（除了一些CDKs）选择性高100倍以上。Phase 1。 |
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| S2621 |
AZD5438AZD5438是一种有效的CDK1/2/9抑制剂，无细胞试验中IC50为16 nM/6 nM/20 nM。对CDK5/6作用效果稍弱，对GSK3β也有抑制作用。Phase 1。 |
(a) HEK-293 cells expressing V5-EXO1 were synchronized in different phases of the cell cycle. EXO1 was immunoprecipitated (IP) with anti-V5 antibody and Western blotted with anti-phospho-Ser (p-SP) or anti-phospho-Thr (p-TP) CDK substrate antibodies, as indicated. “+AZD” indicates cells pre-treated with the CDK inhibitor AZD5438 prior to analysis. (b) HEK-293 cells expressing V5-EXO1, synchronized in G2, were pre-treated with CDK inhibitors, AZD5438 or Roscovitine, prior to analysis of EXO1 phosphorylation by IP-Western.
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| S2735 |
MK-8776 (SCH 900776)MK-8776 (SCH 900776)是一种选择性Chk1抑制剂，无细胞试验中IC50为3 nM，比作用于Chk2选择性高500倍。Phase 2。 |
Hela cell was trypsinized and plated at 30% confluence in DMEM. 16 hours later, MK-8776 (SCH900776) was added at final concentrations of 0, 5, 10 and 25uM. Another 24 hours later, cells were harvested in RIPA with protease and phosphatase inhibitor cocktail. Total protein concentration was measured by BCA method. Lysates equivalent to 20ug total protein were subject to Western Blot, using total- CHK1, pS345-CHK1 and beta-actin (internal control) antibodies. |
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| S2890 |
PF-562271PF-562271是一种有效的，ATP竞争性的，可逆的FAK抑制剂，无细胞试验中IC50为1.5 nM，作用于FAK比作用于Pyk2选择性高10倍左右，比作用于其他蛋白激酶（除了一些CDKs）选择性高100倍以上。 |
VEGF and P450 enzyme production in response to FAK or Src inhibitors. MCF10A cells were cultured in LD collagen gels ?vehicle control (V), 10 uM PF-562271 FAK ATP inhibitor (PF) or Src inhibitor PP2 for 24 h. Cells were also lysed and examined for CYP1A1 or CYP4B1 by immunoblot (B and C) and densitometry (D and E). VEGF data are displayed as the mean normalized to the vehicle control, N = 6, 盨EM, *p < 0.003 vs control (A). P450 data are displayed as the mean relative to GAPDH and normalized to the control. N > 4, ±SEM, *p < 0.05 vs respective control (D and E). |
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| S1487 |
PHA-793887PHA-793887是一种新型有效的CDK2，CDK5和CDK7抑制剂，IC50分别为8 nM， 5 nM 和10 nM，作用于CDK2， 5，和7比作用于CDK1， 4，和9选择性高6倍以上。Phase 1。 |
J558 cells were treated with PHA793887 (0.02–5 umol/L) for 6 hours, after which Western blot analysis was performed to monitor XBP-1s expression. Tub, tubulin.
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| S1572 |
BS-181 HClBS-181 HCl是一种高度选择性的CDK7抑制剂，IC50为21 nM，作用于CDK7比作用于CDK1， 2， 4， 5， 6，和9选择性高40倍以上。 |
Dose-response inhibition of purified human recombinant cyclin-dependent kinase CDK7/cyclin H by inhibitor BS-181 (left panel). Immunoblotting of RNA polymerase II and its phosphorylated form (at Ser5), physiological substrate of CDK7, in MCF-7 cells treated with different doses of inhibitor BS-181 for 24 h (right panel). |
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| S1579 |
Palbociclib (PD0332991) IsethionatePalbociclib (PD0332991) Isethionate是一种高度选择性的CDK4/6抑制剂，无细胞试验中IC50为11 nM/16 nM，对CDK1/2/5，EGFR，FGFR，PDGFR， InsR等没有抑制活性。Phase 3。 |
HT29 cells were treated with DMSO control, 1 uM selumetinib (Sel) or 5 uM PD0332991 (991) for 24 or 48 h after which time cells were lysed, subjected to SDS/PAGE and immunoblotted with the indicated antibodies.
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| S2670 |
A-674563A-674563是一种Akt抑制剂，在无细胞试验中Ki为11 nM，对PKA适度有效，作用于Akt1比作用于PKC选择性高30多倍。 |
B cells were pre-treated with the indicated concentrations of A-674563 for 1h prior to R848 treatment (500 ng/ml). Thymidine incorporation was analyzed 24h later. |
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| S7158 |
abemaciclib mesylate (LY2835219)abemaciclib (LY2835219)是一种有效的，选择性CDK4和CDK6抑制剂，无细胞试验中IC50分别为2 nM和10 nM。Phase 3。 |
HT29 cells were treated with DMSO control, 1 uM selumetinib (Sel), 5 uM PD0332991 (991), 0.3 uM LY2835219 (219) or serum-free (SF) medium for 48 h. Whole cell extracts were prepared, fractionated by SDS/PAGE and analysed by Western blotting with the indicated antibodies. |
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| S2014 |
BMS-265246BMS-265246是一种有效的选择性CDK1/2抑制剂，无细胞试验中IC50为6 nM/9 nM。作用于CDK1/2 比作用于CDK4选择性高25倍。 |
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| S2742 |
PHA-767491PHA-767491是一种有效的，ATP竞争性的，双重Cdc7/CDK9抑制剂，无细胞试验中IC50分别为10 nM和34 nM，比作用于CDK1/2和GSK3-β选择性高20倍左右，比作用于MK2和CDK5选择性高50倍，比作用于PLK1和CHK2选择性高100倍。 |
Viability at 250 nM and CI vs. Fa for U2932 following 24 hours exposure to ABT-199, additional drugs with activity against CDK9, or the combinations. Mean of quadruplicates ± SEM. |
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| S2751 |
Milciclib (PHA-848125)Milciclib (PHA-848125)是一种有效的，ATP竞争性CDK抑制剂，作用于CDK2，IC50为45 nM，作用于CDK2比作用于CDK1， 2， 4， 5和7选择性高3倍以上。 Milciclib (PHA-848125)可通过自噬来诱导细胞死亡。Phase 2。 |
Cell survival curves of A549 cells treated with increasing doses of A-674563, PHA-848125, and H89 2HCl for 72 hours. Cells were incubated with cell proliferation reagent WST-1 for 2 hours and absorbance was read at 450nm. Optical density was then normalized to a 1% DMSO control. The data is presented as the percentage of cell survival relative to the DMSO control ± SEM of three independent trials. Statistical significance was determined with multiple T-tests using the Holm-Sidak method without assuming a consistent SD and is represented by *p<0.05.
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| S2688 |
R547R547是一种有效的，ATP竞争性CDK1/2/4抑制剂，Ki为2 nM/3 nM/1 nM，对CDK7和GSK3α/β作用效果稍弱，而抑制其他激酶活性。Phase 1。 |
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| S7440 |
Ribociclib (LEE011)Ribociclib (LEE011)是一种口服具有活性的，高度特异性CDK4/6抑制剂。Phase 3。 |
Analysis of apoptosis in leukemia cells induced by LEE011. Annexin V staining of cells following 48-h treatment with LEE011 at 2 or 5 µM compared with DMSO controls. Following 5-µM LEE011 treatment, the K562 apoptotic cell percentage was 5.9 ± 0.75 vs. 1.2 ± 0.66% for the DMSO group, P = 0.001; in MV4-11 cells, the apoptotic cell percentage was 24.2 ± 3.06 vs. 0.53 ± 0.40% for the DMSO group, P = 0.005; in U937 cells, the apoptotic cell percentage was 9.9 ± 2.81 vs. 0.57 ± 0.42% for the DMSO group, P = 0.027; in HL-60 cells, the apoptotic cell percentage was 28.23 ± 6.01 vs. 0.9 ± 0.8% for the DMSO group, P = 0.015; in THP-1 cells, the apoptotic cell percentage was 1.76 ± 0.4 vs. 1.56 ± 0.45% for the DMSO group, P = 0.59; in CCRF cells, the apoptotic cell percentage was 13.77 ± 3.16 vs. 1.2 ± 0.36% for the DMSO group, P = 0.019; in NB4 cells, the apoptotic cell percentage was 12.1 ± 1.35 vs. 0.86 ± 0.25% for the DMSO group, P = 0.004; and in SHI-1 cells the apoptotic cell percentage was 12.6 ± 2.81 vs. 1.87 ± 0.75% for the DMSO group, P = 0.017. These analyses were repeated three times. *P < 0.05; **P < 0.01 |
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| S7114 |
NU6027NU6027是一种有效的ATR/CDK抑制剂，抑制CDK1/2， ATR和DNA-PK时，Ki分别为2.5 μM/1.3 μM， 0.4 μM和 2.2 μM ，进入细胞时比6-氨基嘌呤类抑制剂更容易。 |
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| S7357 |
PF-562271 HClPF-562271 HCl是PF-562271的盐酸盐形式，是一种强效的ATP竞争性的可逆的抑制剂，作用于FAK其IC50为1.5 nM。相比较FAK，对Pyk2的效果少了大约十倍，除了CDKs类的蛋白酶，PF-562271 HCl的选择性相比其他蛋白酶大大约100倍。 |
VEGF and P450 enzyme production in response to FAK or Src inhibitors. MCF10A cells were cultured in LD collagen gels ?vehicle control (V), 10 uM PF-562271 FAK ATP inhibitor (PF) or Src inhibitor PP2 for 24 h. Cells were also lysed and examined for CYP1A1 or CYP4B1 by immunoblot (B and C) and densitometry (D and E). VEGF data are displayed as the mean normalized to the vehicle control, N = 6, 盨EM, *p < 0.003 vs control (A). P450 data are displayed as the mean relative to GAPDH and normalized to the control. N > 4, ±SEM, *p < 0.05 vs respective control (D and E). |
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| S8058 |
Riviciclib hydrochloride (P276-00)Riviciclib hydrochloride (P276-00) 是一种新型的CDK1，CDK4和CDK9抑制剂，IC50分别为79 nM， 63 nM和20 nM。Phase 2/3。 |
Predicted anticancer drugs inhibit the growth of neuroendocrine tumor cells. Multi-tyrosine kinase inhibitors sorafenib, sunitinib, regorafenib and cabozantinib effectively inhibit GOT1 cell growth with IC50 values in the micromolar range. Inhibitors of AKT (MK-2206), HDAC (vorinostat), HSP90 (alvespimycin) and CDK4/9 (P276-00) also inhibited GOT1 cell growth at micromolar concentrations, whereas inhibition of PARP1 (veliparib) had no effect. GOT1 cells were treated with anticancer drugs at various concentrations for 4 days. Cell viability was estimated using AlamarBlue®. Data points are the mean values of three individual experiments carried out in triplicate (n=9). Fitting of curves was done in GraphPad Prism software v6.04 using log (inhibitor) vs response nonlinear fit with variable slope. IC50 was interpolated at Y=50 and bars denote ±s.d. |
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| S8727 |
Atuveciclib (BAY-1143572)Atuveciclib (BAY-1143572)是一种有效的、高选择性PTEFb/CDK9抑制剂，对CDK9/CycT的IC50值为13 nM。它对CDK2的IC50是其对CDK9的约100倍。除了CDK家族成员，它还抑制GSK3激酶，对GSK3α和GSK3β的IC50值分别为45 nM和87 nM。 |
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| S7549 |
THZ1 2HClTHZ1是共价的CDK7抑制剂，对位于经典的激酶结构域外端的半胱氨酸残基具有结合能力，对CDK7选择性高。 |
One and three days after differentiation induction, protein level of Myh3 and Myogenin were analyzed by western blot.
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| S7320 |
TG003TG003是一种强效的ATP竞争性的Cdc2-like激酶(Clk)抑制剂，作用于Clk1, Clk2,和Clk4时IC50分别为20 nM, 200 nM,和15 nM。对Clk3, SRPK1, SRPK2, 或者PKC无抑制效果。 |
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| S5316 |
NU2058NU2058 is an inhibitor of CDK2 with IC50 value of 17 μM in an isolated enzyme assay. It also potentiates melphalan (DMF 2.3), and monohydroxymelphalan (1.7), but not temozolomide or ionising radiation. |
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| S7747 |
Ro-3306RO-3306是一种ATP竞争性的选择性 CDK1 抑制剂，Ki 为20 nM，选择性是其他各种人类激酶的15倍多。RO-3306可增强p53介导的 Bax 激活和线粒体的凋亡。 |
HeLa cells were untreated or treated with either colcemid (10 μg/ml for 16 h), RO-3306 (9 μM for 16 h), or both colcemid and RO-3306, as indicated. Cells were then lysed, and proteins were detected by Western analysis.
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| S7992 |
LDC4297 (LDC044297)LDC4297是一种新型的CDK7抑制剂，抑制CDK7的IC50为0.13±0.06 nM，对其他CDKs的IC50范围为10-10,000 nM。 |
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| S8520 |
Senexin ASenexin A是有效的、选择性的CDK8抑制剂，还抑制CDK19，Kd值分别为0.83 μM和0.31 μM。 |
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| S8387 |
MSC2530818MSC2530818是一种CDK8抑制剂，IC50为2.6 nM。具有良好的激酶选择性、生化和细胞效力、微粒体稳定性，并具有生物口服活性。 |
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| S4743 |
WogoninWogonin，在植物中发现的天然活性黄酮类化合物，是CDK9的抑制剂。在抑制CDK9的浓度下，对CDK2、CDK4和CDK6没有抑制作用。也可抑制N-acetyltransferase。 |
Effect of Wogonin on the translocation and transcriptional activity of NFATc1. U2OS cells stably transfected with EGFP-NFATc1, RANKL (100 ng/ml) and different concentrations of Wogonin (5.0, 1.0, 0.1 and 0.0 mM) were added and incubated for 24 h. The IN Cell™ Analyzer 1000 was used to observe the translocation of NFATc1. (A) DMSO was used as a control. RANKL (100 ng/ml) significantly stimulated the translocation of NFATc1; Wogonin (5 mM) significantly decreased the translocation of NFATc1 induced by RANKL (magnification, x200). (B) Statistics showed that Wogonin could decrease the translocation of NFATc1 into the nucleus induced by RANKL in a concentration-dependent manner. RAW264.7 cells were transfected with pGL3-promoter-NFATc1-RE, and then RANKL (100 ng/ml) and different concentrations of Wogonin (5.0, 1.0, 0.1 and 0.0 mM) were added and incubated for 24 h. (C) RANKL significantly increased the transcriptional activity of NFATc1 and Wogonin decreased the transcriptional activity of NFATc1 induced by RANKL in a concentration-dependent manner. n=3; *P<0.05 and ***P<0.001 compared with the RANKL group. NAFTc1, nuclear factor of activated T cells c1; EGFP, enhanced green fluorescent protein; DMSO, dimethylsulfoxide, RANKL, receptor activator of nuclear factor κB ligand; RE, response element.
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| S7793 |
Purvalanol APurvalanol A 是一种有效的，细胞渗透性 CDK 抑制剂，对cdc2-cyclin B，cdk2-cyclin A，cdk2-cyclin E，和 cdk4-cyclin D1的 IC50 分别为 4 nM，70 nM，35 nM，和 850 nM。 |
After 12 h PAB treatment, cells were treated with PAB in the absence and presence of RO-3306 or purvalanol A for 12 h and 36 h. (A) Expressions of p-histone h3 were detected by western blot.
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| S7511 |
LY2857785LY2857785是一种I型可逆的、ATP竞争性的CDK9抑制剂(IC50=0.011 μM)，还可抑制其他转录激酶如CDK8(IC50=0.016 μM)和CDK7 (IC50=0.246 μM)。 |
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| S8100 |
K03861K03861是II型 CDK2 抑制剂，作用于CDK2(WT)，CDK2(C118L)，CDK2(A144C)，和 CDK2(C118L/A144C)的 Kd 分别为 50 nM，18.6 nM，15.4 nM，和 9.7 nM。 |
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| S7509 |
ML167ML167 是一种高度选择性Cdc2-like kinase 4 (Clk4)抑制剂，IC50为136 nM, 其选择性高于相近的激酶Clk1-3和Dyrk1A/1B 10倍。 |
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| S7917 |
KenpaulloneKenpaullone是CDKs的ATP竞争性抑制剂， 它同样也抑制GSK3β，IC50为0.23 μM。 |
Effect of Kenpaullone on GSK-3β and CDKs. (A and B) Naïve CD4+ T cells were stimulated with anti-CD3/CD28 (TCR), TGF-β (5 ng/ml) and IL-6 (20 ng/ml) in the presence of the indicated Kenpaullone (Kenp) concentrations for 30 min (A) or 24 h (A and B).
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| S8652 |
Skp2 inhibitor C1 (SKPin C1)Skp2 inhibitor C1 (SKPin C1)是一种高选择性的Skp2-mediated p27 degradation小分子抑制剂。 |
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| S8161 |
ON123300ON123300是有效的多靶点激酶抑制剂，对CDK4, Ark5, PDGFRβ, FGFR1, RET, Fyn的IC50分别为3.9 nM, 5 nM, 26 nM, 26 nM, 9.2 nM和11nM。 |
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| S5716 |
AbemaciclibAbemaciclib is a cell cycle inhibitor selective for CDK4/6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively. |
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| S7461 |
LDC000067LDC000067 是高度选择性CDK9抑制剂，IC50为44 nM,比作用于CDK2/1/4/6/7的选择性分别高55/125/210/ >227/ >227倍。 |
Inhibition of CDK9 leads to a decrease in RNApol II activity and repetitive element expression. HEK293T cells were treated with DMSO control and the indicated amounts of LDC000067, a CDK9 inhibitor, for a total of 3 h. (A) Immunoblots showing the levels of phosphorylated RNApol II largest subunit (pRPB1), total RPB1 and GAPDH, in response to different doses of CDK9 inhibitor. (B) Quantification of immunoblots from 2 independent experiments in which each condition was performed in duplicates, and in which pRPB1 and total RPB1 protein levels were normalized to GAPDH or as pRPB1/Total RPB1 ratio. (C, D) qRT-PCR analyses show a significant response to CDK9 inhibition of repetitive elements belonging to the LTR (C) and SINE (D) classes. Statistical analyses were performed to compare all groups using a One-way ANOVA followed by Bonforreoni’s multiple comparison test, *P < 0.05, **P < 0.01, #P < 0.0001. |
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| S7636 |
SU9516SU9516是一种3位取代的吲哚酮类CDK抑制剂，对CDK2，CDK1，和CDK4的IC50分别为22 nM，40 nM，和200 nM。 |
a, Porcine blastocysts derived from the SU9516-treated group. Scale bar 100 μM. b, An image of a 7 day SU9516- treated parthenogenetically activated porcine embryo stained with Hoechst 33342. Scale bar 100 μM. c, Tetraploid karyotype from SU9516 treated blastocysts. Scale bar 50 μM. d, Porcine blastocysts derived from the cytochalasin B (CB)-treated group. Scale bar 100 μM. e, An image of a 7 day CB-treated parthenogenetically activated porcine embryo stained with Hoechst 33342. Scale bar 100 μM. f, diploid karyotype from CB treated blastocysts. Scale bar 50 μM
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| S7808 |
AT7519 HClAT7519 HCl是一种多重CDK抑制剂，作用于CDK1，2，4，6 和 9，无细胞试验中IC50为10-210 nM。它对CDK3作用较弱，而对CDK7几乎没有活性。Phase 2。 |
(c) Effect of AT7519 treatment on RNA pol II occupancy at the PRCC gene. MM1.S cells were treated with either DMSO vehicle (blue) or 2 μM AT7519 (brown) for 6 h, followed by RNA pol II ChIP-seq analysis. Twenty-fold magnifications of the rpm/bp scale of these gene tracks are shown in the right panel to show the difference in reads for elongating RNA pol II. TR, RNA pol II traveling ratio.
(d) Genome-wide binding average RNA pol II (ChIP-seq) on active promoters and gene bodies following treatment of MM1.S cells with DMSO vehicle (blue) or 2 μM of AT7519 (brown) for 6 h. Magnification of the rpm/bp scale at gene bodies is shown in the inset. The inset includes RNA polymerase II traveling ratio distributions (TR, mean) derived from MM1.S cells treated with DMSO (blue) or 2 μM AT7519 (red).
(e) Chemical structures of the pan-CDK inhibitor AT7519 and its biotinylated counterpart bio-AT7519.
(f) In vitro kinase assays with recombinant cyclin T-CDK9 complex in the presence of increasing concentrations of AT7519 or bio-AT7519. The derived IC50 values for each compound are shown.
(g) Effect of AT7519 and bio-AT7519 on MM1.S cell proliferation. Cells were treated with varying concentrations of drug for 72 h as indicated. The derived EC50 values for each compound are shown.
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| S8719 |
AZD4573AZD4573是有效的CDK9抑制剂（IC50<0.004 μM），具有高选择性。 |
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| S7547 |
XL413 (BMS-863233)XL413 (BMS-863233) 是强效的选择性的cell division cycle 7 homolog (CDC7) kinase抑制剂，IC50为3.4 nM,其选择性分别超过 CK2, Pim-1 和pMCM2选择性的 63-, 12-和35-倍。 Phase 1/2。 |
The protein levels of p-MCM2 and p-ERK in NOK, HN6 and Cal27 cells treated with 0, 10 and 20 μMXL413 were detected by western blotting.
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| S8840 |
SEL120(SEL120-34A) hydrochlorideSEL120(SEL120-34,SEL120-34A)是一种新型的CDK8抑制剂，对CDK8和CDK19的IC50值分别为4.4 nM和10.4 nM。 |
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