CDK

信号通路图

研究领域

抑制剂选择性比较
溶解性比较

目录号	产品目录	溶解度(25°C)
目录号	产品目录	水	DMSO	酒精
S1116	Palbociclib (PD-0332991) HCl	30 mg/mL	3 mg/mL	<1 mg/mL
S1153	Roscovitine (Seliciclib,CYC202)	<1 mg/mL	71 mg/mL	6 mg/mL
S1145	SNS-032 (BMS-387032)	<1 mg/mL	76 mg/mL	<1 mg/mL
S2768	Dinaciclib (SCH727965)	<1 mg/mL	26 mg/mL	8 mg/mL
S1230	Flavopiridol (Alvocidib)	<1 mg/mL	15 mg/mL	8 mg/mL
S8727	Atuveciclib (BAY-1143572)	<1 mg/mL	77 mg/mL	<1 mg/mL
S5716	Abemaciclib	<1 mg/mL	6 mg/mL	8 mg/mL
S5316	NU2058	<1 mg/mL	49 mg/mL	49 mg/mL
S8652	Skp2 inhibitor C1 (SKPin C1)	<1 mg/mL	93 mg/mL	<1 mg/mL
S1524	AT7519	<1 mg/mL	10 mg/mL	<1 mg/mL
S2679	Flavopiridol HCl	<1 mg/mL	88 mg/mL	<1 mg/mL
S1249	JNJ-7706621	<1 mg/mL	79 mg/mL	<1 mg/mL
S2621	AZD5438	<1 mg/mL	74 mg/mL	74 mg/mL
S2735	MK-8776 (SCH 900776)	<1 mg/mL	3 mg/mL	<1 mg/mL
S1487	PHA-793887	<1 mg/mL	72 mg/mL	72 mg/mL
S1572	BS-181 HCl	3 mg/mL	83 mg/mL	22 mg/mL
S1579	Palbociclib (PD0332991) Isethionate	10 mg/mL	<1 mg/mL	<1 mg/mL
S2670	A-674563	72 mg/mL	72 mg/mL	18 mg/mL
S7158	abemaciclib mesylate (LY2835219)	100 mg/mL	83 mg/mL	24 mg/mL
S2014	BMS-265246	<1 mg/mL	20 mg/mL	<1 mg/mL
S2742	PHA-767491	<1 mg/mL	24 mg/mL	<1 mg/mL
S2751	Milciclib (PHA-848125)	<1 mg/mL	92 mg/mL	<1 mg/mL
S2688	R547	<1 mg/mL	60 mg/mL	<1 mg/mL
S7440	Ribociclib (LEE011)	<1 mg/mL	7 mg/mL	<1 mg/mL
S7114	NU6027	<1 mg/mL	50 mg/mL	3 mg/mL
S8058	P276-00	88 mg/mL	88 mg/mL	7 mg/mL
S7549	THZ1 2HCl	<1 mg/mL	100 mg/mL	<1 mg/mL
S7320	TG003	<1 mg/mL	6 mg/mL	<1 mg/mL
S7747	Ro-3306	<1 mg/mL	13 mg/mL	<1 mg/mL
S7992	LDC4297 (LDC044297)	27 mg/mL	86 mg/mL	86 mg/mL
S8520	Senexin A	<1 mg/mL	54 mg/mL	54 mg/mL
S8387	MSC2530818	<1 mg/mL	68 mg/mL	68 mg/mL
S4743	Wogonin	<1 mg/mL	56 mg/mL	3 mg/mL
S7793	Purvalanol A	<1 mg/mL	60 mg/mL	13 mg/mL
S7511	LY2857785	<1 mg/mL	23 mg/mL	42 mg/mL
S8100	K03861	<1 mg/mL	100 mg/mL	15 mg/mL
S7509	ML167	<1 mg/mL	67 mg/mL	13 mg/mL
S7917	Kenpaullone	<1 mg/mL	65 mg/mL	<1 mg/mL
S8161	ON123300	<1 mg/mL	29 mg/mL	<1 mg/mL
S7461	LDC000067	<1 mg/mL	74 mg/mL	<1 mg/mL
S7636	SU9516	<1 mg/mL	48 mg/mL	12 mg/mL
S7808	AT7519 HCl	43 mg/mL	52 mg/mL	28 mg/mL
S7547	XL413 (BMS-863233)	46 mg/mL	<1 mg/mL	<1 mg/mL

特异性亚型抑制剂

CDK抑制剂（43）
新CDK产品

产品目录	产品描述	文献引用	实验数据
S1116	Palbociclib (PD-0332991) HCl Palbociclib (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。	Cell, 2018, 174(5):1127-1142 P Natl Acad Sci USA, 2011, 108(20):8414-9 Int J Cancer, 2013, 133(10):2341-50	PD-0332991 causes inhibition of proliferation of EAC cells in a dose-dependent manner. Western blots showing the phosphorylation status of pRB at Ser780 and Ser795 after incubation with 125 nmol/L PD-0332991 for 24 and 72 hours. Reduction in cyclin A expression and the expression of RB2 (p130) tumor suppressor 72 hours after PD-0332991 treatment are shown (bottom). Total pRB (RB1) and actin are loading controls and T293 cell lysate (293) is a positive control for total pRB and phospho-pRB (Ph-RB). E, anchorage-independent growth of the 3 cell lines in the presence or absence (Cnt) of 125 nmol/L PD-0332991 for 3 weeks.
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。	Cell, 2018, 174(5):1127-1142 Circ Res, 2012, 111(2):201-11 J Hematol Oncol, 2014, 7(1):53	In vitro inhibition of mouse corticotroph tumor cells by R-roscovitine. (A) Treatment of ACTH-secreting AtT20 cells with R-roscovitine (1-2 × 10-5 μM) led to decreased number of viable cells at 24 and 48 h, as depicted by Wst-1 proliferation assay (mean ± SE; P < 0.01). (B) Western blot of protein extracts derived from AtT20 cells treated with vehicle or R-roscovitine. (C) R-roscovitine treatment (10 μM) for 48 h induced senescence as indicated by increased β-gal expression. (D) ACTH concentration by radioimmunoassays of culture medium from AtT20 cells treated with vehicle or R-roscovitine (mean ±SE; P < 0.01 and ***P < 0.001). (E) Western blot of protein extracts derived from AtT20 cells treated with R-roscovitine. Vehicle is 0.2% DMSO.
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。	Nat Commun, 2017, 8:14290 Leukemia, 2015, 10.1038/leu.2015.99 Proc Natl Acad Sci USA, 2013, 110(33):13588-93	For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of SNS-032 by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 μM HCl and 0.1% Nonidet-40) was added to dissolve the formazan. The absorbance of each well was measured by ELx808 (BioTek, Winooski, VT) or Wallac Victor2 (Perkin-Elmer Life Sciences, Boston, MA) Microplate Reader. Viable cells are presented as percent of control, vehicle-treated cells.
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。Phase 3。	J Clin Invest, 2014, 124(8):3325-38 Leukemia, 2015, 10.1038/leu.2015.99 Oncogene, 2016, 10.1038/onc.2016.471	(a) Western blot for RALB-GTP, total RALB and GAPDH proteins in KG1 AML cells treated for 8 h with DMSO or dinaciclib (representative of three independent experiments).
S1230	Flavopiridol (Alvocidib) Flavopiridol (Alvocidib)与ATP竞争性抑制CDKs，包括CDK1， CDK2， CDK4和CDK6，CDK9，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。Phase 1/2。	Nat Med, 2015, 10.1038/nm.3855 Leukemia, 2014, 28(3):629-41 Leukemia, 2015, 10.1038/leu.2015.99	(A) After mitotic arrest and treatment with the proteasome inhibitor MG132, HeLa cells were treated with the indicated kinase inhibitors The cells were harvested, and the lysates were separated by SDS-PAGE and immunoblotted for phosphorylated RV[S/T]F (p-RV[S/T]F, top). The blot was quantified using ImageJ software and normalized to the mitotic sample (bottom). MLN8054, Aurora A and Aurora B inhibitor; ZM447439 and hesperadin, Aurora B inhibitors; BI2536, PLK1 inhibitor; flavopiridol, CDK1 inhibitor. n = 3. **P < 0.01, paired Student’s t test.
S8727^New	Atuveciclib (BAY-1143572) Atuveciclib (BAY-1143572) is potent and highly selective PTEFb/CDK9 inhibitor with IC50 values of 13 nM for CDK9/CycT and the ratio of IC50 values for CDK2/CDK9 is about 100. Outside the CDK family, It inhibits GSK3 kinase with IC50 values of 45 nM and 87 nM for GSK3α and GSK3β respectively.
S5716^New	Abemaciclib Abemaciclib is a cell cycle inhibitor selective for CDK4/6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively.
S5316^New	NU2058 NU2058 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.
S8652^New	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。
S1524	AT7519 AT7519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。Phase 2。	Nat Biotechnol, 2014, 32(1):92-6 Cancer Lett, 2014, 342(1):159-66 AIDS, 2014, 28(15):2213-22	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.
S2679	Flavopiridol HCl Flavopiridol 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。	Nat Commun, 2016, 7:12044 Leukemia, 2014, 28(3):629-41 Proc Natl Acad Sci USA, 2011, 108(20):8414-9	(C) In vivo treatment of Tg:Pomc-Pttg;Pomc-eGFP embryos with small-molecule CDK inhibitors (50μM) 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.)
S1249	JNJ-7706621 JNJ-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。	Cell Death Differ, 2017, 24(1):38-48 Oncogene, 2014, 10.1038/onc.2014.351 Mol Cancer Ther, 2014, 13(3):662-74	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.
S2621	AZD5438 AZD5438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。	Nat Commun, 2014, 5:3561 J Hematol Oncol, 2018, 10.1186/s13045-018-0563-y Mol Cancer Ther, 2014, 13(3):662-74	(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.
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。	Cell Death Dis, 2015, 6:e1947 Acta Pharmacol Sin, 2017, 38(4):513-523 Oncotarget, 2016, 7(51):85033-85048	MCF7 cells were seeded in 60 mm dishes and were pretreated with the specified inhibitor 1 h before stimulation with either vehicle or doxorubicin. Twenty-four hours after treatment, cells were collected and immunoblotted for nSMase2 and actin.
S1487	PHA-793887 PHA-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。	Mol Cancer Ther, 2014, 13(3):662-74 Anticancer Agents Med Chem, 2011, 11(5):418-26	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.
S1572	BS-181 HCl BS-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。	Cancer Res, 2016, 10.1158/0008-5472.CAN-16-0774 Arthritis Rheumatol , 2014, 66(6):1537-46 Clin Exp Med, 2015, 15(3):269-75	Relative sensitivity of UKF-NB-3 and UKF-NB-3rSNS-032300nM to the CDK2, 7, and 9 inhibitor seliciclib, the CDK7 inhibitor LDC000067, the CDK9 inhibitor BS-181, or the CDK 1,2,4,6,7, and 9 inhibitor alvocidib.
S1579	Palbociclib (PD0332991) Isethionate Palbociclib (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。	Science, 2016, 354(6315) Nucleic Acids Res, 2013, 41(22):10334-44 Proc Natl Acad Sci USA, 2013, 110(10):4015-20	(C) In vivo treatment of Tg:Pomc-Pttg;Pomc-eGFP embryos with small-molecule CDK inhibitors (50μM) 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.)
S2670	A-674563 A-674563是一种Akt抑制剂，在无细胞试验中K_i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。	Cancer Cell Int, 2017, 10.1186/s12935-017-0396-8 Eur J Pharmacol, 2015, 764:208-214 Microvasc Res, 2015, 101:72-81	Cell survival was determined using a WST-1 assay in the human lung cancer cells A549 A. and NCI-H358 B. following treatment with either an AKT1 specific inhibitor, A-674563 (black circle and line) or a pan-AKT inhibitor MK-2206 (gray square and line). *p < 0.05.
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。	Nat Commun, 2016, 10.1038/ncomms10660 Clin Cancer Res, 2017, 23(22):6946-6957 J Urol, 2015, 195(3):771-9	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.
S2014	BMS-265246 BMS-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。
S2742	PHA-767491 PHA-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。	Cell, 2018, 174(5):1127-1142 Leukemia, 2015, 10.1038/leu.2015.99	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.
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。Phase 2。	Mol Cancer Ther, 2014, 13(3):662-74 Mol Cancer Ther, 2014, 13(3):662-74	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.
S2688	R547 R547是一种有效的，ATP竞争性CDK1/2/4抑制剂，K_i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。
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。	Nature, 2018, 553(7686):91-95 Cancer Res, 2016, 76(22):6723-6734 Cancer Cell Int, 2017, 10.1186/s12935-017-0405-y	IB analysis of whole cell lysates derived from mouse CT26 or 4T1 tumor cell lines treated with or without the CDK4/6 inhibitor, ribociclib.
S7114	NU6027 NU6027是一种有效的ATR/CDK抑制剂，抑制CDK1/2， ATR和DNA-PK时，K_i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。
S8058	P276-00 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。	Mod Pathol, 2016, 10.1038/modpathol.2016.48.	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.
S7549	THZ1 2HCl THZ1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。
S7320	TG003 TG003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。
S7747	Ro-3306 RO-3306是一种ATP竞争性的选择性 CDK1 抑制剂，K_i 为20 nM，选择性是其他各种人类激酶的15倍多。	Nature, 2016, 539(7627):54-58 J Cell Biol, 2015, 209(2):221-34 Arthritis Rheumatol , 2016, 68(5):1222-32	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.
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。
S8520	Senexin A Senexin 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。
S8387	MSC2530818 MSC2530818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。
S4743	Wogonin Wogonin，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。	Exp Ther Med, 2015, 10(3):1066-1070	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.
S7793	Purvalanol A Purvalanol 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。	J Biol Chem, 2016, 10.1074/jbc.M116.722751	（A）HeLa cells were treated with Nocodazole for 8 hours and then fixed. Before the cells were stained with phospho-specific antibody against S119 of Ajuba, they were pre-incubated with PBS (no peptide control), or non-phosphorylated (control) peptide, or the phosphorylated peptide used for immunizing rabbits. CDK1 inhibitors Purvalanol A (10 μM) together with MG132 (25 μM) were added 2 h before the cells were fixed (bottom two rows).（B）Experiments were done similarly as in (A) with phospho-specific antibody against Ser175 of Ajuba.
S7511	LY2857785 LY2857785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)。
S8100	K03861 K03861是II型 CDK2 抑制剂，作用于CDK2(WT)，CDK2(C118L)，CDK2(A144C)，和 CDK2(C118L/A144C)的 K_d 分别为 50 nM，18.6 nM，15.4 nM，和 9.7 nM。
S7509	ML167 ML167 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。
S7917	Kenpaullone Kenpaullone是CDKs的ATP竞争性抑制剂，它同样也抑制GSK3β，IC50为0.23 μM。	Biochem Biophys Res Commun, 2013, 435(3):378-84	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).
S8161	ON123300 ON123300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。
S7461	LDC000067 LDC000067 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。	Hum Mol Genet, 2017, 10.1093/hmg/ddx233 Oncotarget, 2016, 7(36):58051-58064	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.
S7636	SU9516 SU9516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。	Biotechnol Lett, 2017, 39(7):951-957	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
S7808	AT7519 HCl AT7519 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。	Nat Biotechnol, 2014, 32(1):92-6	(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.
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。	Exp Cell Res, 2015, 339(2):289-99	Effects of XL413 plus pirfenidone on 10T1/2 cells morphology, proliferation and TGF-β1-induced α-SMA expression. Cells were exposed to control, XL413 (10 μM), pirfenidone (1 mg/ml) or XL413 plus pirfenidone. (G) Laser confocal scanning was used for visualization of α-SMA protein expression and cellular morphological changes.

研究领域

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CDK

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研究领域

特异性亚型抑制剂