ALK
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) | ||
|---|---|---|---|---|
| 水 | DMSO | 酒精 | ||
| S1068 | Crizotinib (PF-02341066) | <1 mg/mL | 9 mg/mL | <1 mg/mL |
| S1108 | TAE684 (NVP-TAE684) | <1 mg/mL | 3 mg/mL | <1 mg/mL |
| S2762 | Alectinib (CH5424802) | <1 mg/mL | 0.5 mg/mL | <1 mg/mL |
| S7083 | Ceritinib (LDK378) | <1 mg/mL | 20 mg/mL | 3 mg/mL |
| S7000 | AP26113-analog (ALK-IN-1) | <1 mg/mL | 45 mg/mL | 106 mg/mL |
| S8700 | TP0427736 HCl | <1 mg/mL | 67 mg/mL | <1 mg/mL |
| S5232 | Alectinib hydrochloride | <1 mg/mL | 2 mg/mL | <1 mg/mL |
| S2703 | GSK1838705A | <1 mg/mL | 107 mg/mL | <1 mg/mL |
| S7106 | AZD3463 | <1 mg/mL | 24 mg/mL | <1 mg/mL |
| S8054 | ASP3026 | <1 mg/mL | 14 mg/mL | <1 mg/mL |
| S7998 | Entrectinib (RXDX-101) | <1 mg/mL | 100 mg/mL | 75 mg/mL |
| S8583 | TPX-0005 | <1 mg/mL | 70 mg/mL | 10 mg/mL |
| S8229 | Brigatinib (AP26113) | <1 mg/mL | 1 mg/mL | 43 mg/mL |
| S8511 | Belizatinib (TSR-011) | <1 mg/mL | 100 mg/mL | 100 mg/mL |
| S7148 | ML347 | <1 mg/mL | 10 mg/mL | <1 mg/mL |
| S7536 | Lorlatinib (PF-6463922) | <1 mg/mL | 81 mg/mL | 30 mg/mL |
| S8230 | Ensartinib (X-396) | <1 mg/mL | 100 mg/mL | 100 mg/mL |
- ALK抑制剂（17）
- 新ALK产品
| 产品目录 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S1068 |
Crizotinib (PF-02341066)Crizotinib (PF-02341066)是一种有效的c-Met和ALK抑制剂，在细胞试验中IC50分别为11 nM 和 24 nM。 |
(c) Western blot analyses of p-Akt (Ser473) and p-S6RP (Ser235 and Ser236) in two RCT-E565 transplanted tumors treated with vehicle or PF02341066. Samples were isolated 4 h after the last dose from mice treated with PF02341066 for 3 d. (d) Responses of RCT-E565 transplanted tumors in athymic mice to PF02341066 or vehicle. Data are means ±s.e.m. (each group, n = 6). *P < 0.005, **P < 0.001 (Student,s t test). |
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| S1108 |
TAE684 (NVP-TAE684)TAE684 (NVP-TAE684)是一种有效的，选择性ALK抑制剂，在无细胞试验中IC50为3 nM，作用于ALK比作用于InsR选择性高100倍。 |
(A) H3122 xenografts harboring the EML4-ALK translocation were treated with control vehicle or the ALK inhibitor, TAE-684, for 2 days; the tumors were excised and lysates were prepared. The TIMM results for the control and treated animals are shown. (B) H3122 cells were treated in the presence or absence of TAE-684 (100 nM) for 6 hours in the presence or absence of the indicated ligands [EGF (50 ng/mL), IGF1 (50 ng/mL), and HGF (50 ng/mL)]. Extracts were probed with the indicated antibodies. |
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| S2762 |
Alectinib (CH5424802)Alectinib (CH5424802)是一种有效的ALK抑制剂，在无细胞试验中IC50为1.9 nM，对L1196M突变型敏感，对ALK比PF-02341066， NVP-TAE684和PHA-E429选择性高。 |
Immunoblot analysis of full-length DCTN1-ALK proteins. An expression vector encoding DCTN1-ALK cDNA was introduced into H1299 lung cancer cells, which do not express endogenous ALK. The transfectants were then exposed to crizotinib and alectinib. Levels of phosphorylation at tyrosine 1604 were determined 24 hours after treatment with 0, 0.2, 1.0, or 5.0 μM of each drug.
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| S7083 |
Ceritinib (LDK378)Ceritinib (LDK378)是一种有效的ALK抑制剂，在无细胞试验中IC50为0.2 nM，与作用于IGF-1R和InsR相比，选择性分别高40和35倍。Phase 3。 |
Quantitation of crystal violet uptake by ORF-expressing cells exposed to crizotinib (CRZ) or ceritinib (CER) normalized to Lac Z. Mean and SE are shown for six (CRZ) or four (CER) independent experiments of three replicates each.
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| S7000 |
AP26113-analog (ALK-IN-1)AP26113-analog (ALK-IN-1) 是AP26113的类似物，是有效的、选择性的ALK抑制剂，同时也是EGFR的抑制剂。 |
Several ALK inhibitors effectively inhibit the growth of CD74–ROS1–addicted Ba/F3 cells. A, Ba/F3 cells expressing CD74–ROS1 (clone #6) were seeded in 96-well plates and treated with the indicated concentration of crizotinib, ceritinib, AP26113, ASP3026, or alectinib for 72 hours. Cell viability was analyzed using the CellTiter-Glo Assay. B, IC50 values (nmol/L) of Ba/F3 cell lines expressing CD74–ROS1 (clone #6) against various ALK inhibitors are shown. Average IC50 values against crizotinib, ceritinib, or AP26113 were calculated from the three independent experiments. IC50 values against ASP3026 and alectinib were calculated from the single experiment. C, inhibition of phospho-ROS1 by various ALK inhibitors in Ba/F3 models. CD74–ROS1–expressing Ba/F3 cells were exposed to increasing concentrations of crizotinib, ceritinib, AP26113, ASP3026, or alectinib for 3 hours. Cell lysates were immunoblotted to detect the indicated proteins. |
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| S8700New |
TP0427736 HClTP0427736 is a potent inhibitor of ALK5 kinase activity with an IC50 of 2.72 nM and this effect is 300-fold higher than the inhibitory effect on ALK3 (IC50 = 836 nM for ALK3). It also inhibits Smad2/3 phosphorylation in A549 cells induced by TGF-β1 with an IC50 value of 8.68 nM. |
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| S5232New |
Alectinib hydrochlorideAlectinib是一种选择性抑制ALK酪氨酸激酶的口服药物，IC50为1.9 nM。 |
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| S2703 |
GSK1838705AGSK1838705A是一种有效的IGF-1R抑制剂，IC50为2.0 nM，适度有效作用于IR和ALK，IC50分别为1.6 nM和0.5 nM，对其他蛋白激酶几乎没有作用活性。 |
GSK1838705A suppresses glioma tumor growth and induces apoptosis in vivo. (A) Following inoculation of U87MG cells, formulated vehicle control or GSK1838705A (4 and 8 mg/kg) was injected into the corresponding group of nude mice (n=6/group) once daily. The tumors were measured every other day for 11 days and the tumor volumes were calculated. Starting on day 7, the differences between the treatment groups (4 and 8 mg/kg) and the vehicle control group were significant (P<0.05). (B) Body weights of the mice during the course of treatment were measured as an indication of significant cytotoxic effects. The data are expressed as the mean ± standard deviation. No significant differences are observed between any two of the groups during the course of treatment. (C) At the end of treatment, the tumors were harvested. GSK1838705A (8 mg/kg) induced the apoptosis of tumor cells in vivo, determined using a TUNEL assay (green) and nuclear staining with Hoechst (blue). Representative images are shown (magnification, ×40). TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling. |
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| S7106 |
AZD3463AZD3463是一种新型的，口服有效的ALK抑制剂， Ki为0.75 nM，也等效抑制IGF1R 。 |
(E) Immunoblot analysis of lysates of A4573 and TC32 cells following exposure to media only (Control, C); ST/V and V/ST with (+) or without (-) 20 nM AZD3463 using antibodies against ALK, IGF-1R, STAT3 (Y705), p-STAT3, AKT, p-AKT (S473), MAPK, p-MAPK (p42/44). |
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| S8054 |
ASP3026ASP3026 是一种新型选择性ALK 抑制剂，其IC50 为3.5 nM.Phase 1。 |
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| S7998 |
Entrectinib (RXDX-101)Entrectinib (RXDX-101)是一种口服生物可利用的泛-TrkA/B/C，ROS1 和 ALK 抑制剂，IC50范围为 0.1~1.7 nM。Phase 2。 |
(A) We transfected the EGFP/Eluc gene into KM12SM cells to establish KM12SM/Eluc cells. KM12SM/Eluc cells were inoculated into the brain of SCID mice. The mice were treated daily with or without entrectinib (15 mg/kg) for 37 days until the bioluminescence increased. Mean ± SE of total flux are shown in the lower panel. Then, the entrectinib-treated brain tumor was harvested at the point indicated by the orange triangle and cultured in vitro. The expanded tumor cells were named KM12SM-ER. (B) The sensitivity of KM12SM-ER and KM12SM cells to entrectinib was determined through cell viability assays, using a CCK-8 kit. The data (mean ± standard deviation [SD] of triplicate cultures) shown are representative of three independent experiments with similar results. (C) Tumor cells were treated with entrectinib (10 nmol/L) for 4 h or c-PARP for 48 h, and harvested lysates were assessed by western blotting. Data shown are representative of three independent experiments with similar results.
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| S8583 |
TPX-0005TPX-0005是一种新型的ALK/ROS1/TRK抑制剂，对WT ALK、ALK(G1202R)、ALK(L1196M)的IC50分别为1.01 nM、1.26 nM、1.08 nM；同时也是一种有效的SRC抑制剂，IC50为5.3 nM。 |
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| S8229 |
Brigatinib (AP26113)Brigatinib (AP26113)是一种有效的、选择性的ALK抑制剂，IC50=0.6 nM；也是ROS1抑制剂，IC50=0.9 nM。它还能以相对较低的效力抑制FLT3、FLT3(D835Y)、EGFR。 |
Immunoblotting analysis of H3122 and H3122-CER cells showing that brigatinib did not inhibit EGFR phosphorylation (p-EGFR). Total EGFR (t-EGFR) is also shown. Actin was used as a loading control. The cells were treated with brigatinib for 2 hours.
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| S8511 |
Belizatinib (TSR-011)Belizatinib (TSR-011)是一种有效的ALK（IC50=0.7 nM）和tropomyosin receptor kinase (TRK) （IC50<3 nM）抑制剂。 |
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| S7148 |
ML347ML347 是一种选择性的BMP receptor抑制剂，其作用于ALK2的IC50为 32 nM ,选择性高于ALK3 300倍。 |
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| S7536 |
Lorlatinib (PF-6463922)PF-06463922是一个强效的，双重 ALK/ ROS1的抑制剂，对ROS1, ALK (WT), 以及ALK (L1196M)的Ki分别为<0.02 nM, <0.07 nM, 和0.7 nM。Phase 1。 |
Sub-G1 and cell cycle phase distribution of NBLW and NBLW-R cells treated for 24 hours with DMSO, 1× or 10× the respective GI 50 concentrations of PF-06463922.
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| S8230 |
Ensartinib (X-396)Ensartinib (X-396)是一种新型的、有效的、特异的ALK酪氨酸激酶抑制剂，在Ambit assay中对ALK的IC50小于4 nM。 |
