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抑制剂选择性比较

ALK产品

所有产品 ALK抑制剂(18) 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) 克唑替尼是一种有效的c-Met和ALK抑制剂，在细胞试验中IC50分别为11 nM 和 24 nM。它同时也是有效的ROS1抑制剂，其Ki值小于0.025 nM。	Int J Mol Sci, 215, 16(1):2174-86 Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 36(2):179-193	(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).
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。	Cancer Cell, 2019, 36(2):179-193 Cell, 2019, 36(2):179-193 Leuk Res, 2019, 78:12-20	(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.
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。	Drug Metab Dispos, 2019, 47(7):699-709 Transl Oncol, 2019, 12(1):116-121 Anticancer Res, 2019, 39(7):3579-3584	Sensitivity of the H3122 cell line to ALK inhibitors (crizotinib and alectinib). To examine the sensitivity of ALK inhibitors, used an MTT assay. The experiment was performed in triplicate. (A) Growth inhibitory effect of crizotinib. The H3122 cell line was sensitive to crizotinib under a normoxic state, compared with a hypoxic state. The graphs, mean of independent triplicate experiments; error bars, SD. (B) IC50 of ALK inhibitors. The IC50 values of both inhibitors in the H3122 cell lines were significantly higher under hypoxia than under normoxia (crizotinib, P=0.028 and alectinib, P=0.0035). *P<0.05.
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。	Nature, 2019, 10.1038/s41586-019-1472-0 Cancer Cell, 2019, 36(2):179-193 Cell, 2019, 36(2):179-193	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.
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。	Clin Cancer Res, 2015, 21(1):166-74 Clin Cancer Res, 2014, 20(22):5686-96 Jpn J Clin Oncol, 2014, 44(10):963-8	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.
S6513^New	HG-14-10-04 HG-14-10-04是ALK抑制剂。
S6505^New	X-376 X-376是ALK抑制剂，对治疗非小细胞性肺癌有潜在疗效。
S2703	GSK1838705A GSK1838705A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。	Cell, 2019, 36(2):179-193 Cancer Cell, 2019, 36(2):179-193 Cell Chem Biol, 2019, 10.1016/j.chembiol.2019.06.003	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.
S7106	AZD3463 AZD3463是一种新型的，口服有效的ALK抑制剂， K_i为0.75 nM，也等效抑制IGF1R 。	PLoS One, 2015, 10(11):e0142704	(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).
S8054	ASP3026 ASP3026 是一种新型选择性ALK 抑制剂，其IC50 为3.5 nM.Phase 1。
S8700	TP0427736 HCl TP0427736是一种有效的ALK5 kinase抑制剂，IC50为2.72 nM，对ALK3的IC50为836 nM。在A549细胞中，它还能抑制TGF-β1诱导的Smad2/3磷酸化，IC50为8.68 nM。
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。	Mol Cancer Ther, 2019, 18(6):1137-1148 J Drug Target, 2019, 27(4):442-450 Clin Cancer Res, 2018, 24(10):2357-2369	Tumor cells were treated with entrectinib (10 nmol/L) for 4 hours or c-PARP for 48 hours, and harvested lysates were assessed by Western blotting. Data shown are representative of three independent experiments with similar results.
S8583	Repotrectinib (TPX-0005) TPX-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。
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。	Cell Syst, 2019, 8(2):97-108 Clin Cancer Res, 2018, 24(17):4162-4174 Cancer Sci, 2018, 109(10):3149-3158	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.
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。
S7148	ML347 ML347 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。	Stem Cells Int, 2019, 2019:4254759 Stem Cells International, 2019, 10.1155/2019/4254759
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K_i分别为<0.02 nM, <0.07 nM, 和0.7 nM。Phase 1。	Nature, 2019, 10.1038/s41586-019-1472-0 Invest New Drugs, 2019, 10.1007/s10637-019-00795-3 Biochem Biophys Res Commun, 2019, 511(2):260-265	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.
S5232	Alectinib hydrochloride Alectinib是一种选择性抑制ALK酪氨酸激酶的口服药物，IC50为1.9 nM。

产品目录	产品描述	文献引用	实验数据
S1068	Crizotinib (PF-02341066) Crizotinib (PF-02341066) 克唑替尼是一种有效的c-Met和ALK抑制剂，在细胞试验中IC50分别为11 nM 和 24 nM。它同时也是有效的ROS1抑制剂，其Ki值小于0.025 nM。	Int J Mol Sci,215, 16(1):2174-86 Cell,2019, 36(2):179-193 Cancer Cell,2019, 36(2):179-193	(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).
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。	Cancer Cell,2019, 36(2):179-193 Cell,2019, 36(2):179-193 Leuk Res,2019, 78:12-20	(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.
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。	Drug Metab Dispos,2019, 47(7):699-709 Transl Oncol,2019, 12(1):116-121 Anticancer Res,2019, 39(7):3579-3584	Sensitivity of the H3122 cell line to ALK inhibitors (crizotinib and alectinib). To examine the sensitivity of ALK inhibitors, used an MTT assay. The experiment was performed in triplicate. (A) Growth inhibitory effect of crizotinib. The H3122 cell line was sensitive to crizotinib under a normoxic state, compared with a hypoxic state. The graphs, mean of independent triplicate experiments; error bars, SD. (B) IC50 of ALK inhibitors. The IC50 values of both inhibitors in the H3122 cell lines were significantly higher under hypoxia than under normoxia (crizotinib, P=0.028 and alectinib, P=0.0035). *P<0.05.
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。	Nature,2019, 10.1038/s41586-019-1472-0 Cancer Cell,2019, 36(2):179-193 Cell,2019, 36(2):179-193	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.
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。	Clin Cancer Res,2015, 21(1):166-74 Clin Cancer Res,2014, 20(22):5686-96 Jpn J Clin Oncol,2014, 44(10):963-8	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.
S6513^New	HG-14-10-04 HG-14-10-04是ALK抑制剂。
S6505^New	X-376 X-376是ALK抑制剂，对治疗非小细胞性肺癌有潜在疗效。
S2703	GSK1838705A GSK1838705A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。	Cell,2019, 36(2):179-193 Cancer Cell,2019, 36(2):179-193 Cell Chem Biol,2019, 10.1016/j.chembiol.2019.06.003	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.
S7106	AZD3463 AZD3463是一种新型的，口服有效的ALK抑制剂， K_i为0.75 nM，也等效抑制IGF1R 。	PLoS One,2015, 10(11):e0142704	(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).
S8054	ASP3026 ASP3026 是一种新型选择性ALK 抑制剂，其IC50 为3.5 nM.Phase 1。
S8700	TP0427736 HCl TP0427736是一种有效的ALK5 kinase抑制剂，IC50为2.72 nM，对ALK3的IC50为836 nM。在A549细胞中，它还能抑制TGF-β1诱导的Smad2/3磷酸化，IC50为8.68 nM。
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。	Mol Cancer Ther,2019, 18(6):1137-1148 J Drug Target,2019, 27(4):442-450 Clin Cancer Res,2018, 24(10):2357-2369	Tumor cells were treated with entrectinib (10 nmol/L) for 4 hours or c-PARP for 48 hours, and harvested lysates were assessed by Western blotting. Data shown are representative of three independent experiments with similar results.
S8583	Repotrectinib (TPX-0005) TPX-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。
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。	Cell Syst,2019, 8(2):97-108 Clin Cancer Res,2018, 24(17):4162-4174 Cancer Sci,2018, 109(10):3149-3158	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.
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。
S7148	ML347 ML347 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。	Stem Cells Int,2019, 2019:4254759 Stem Cells International,2019, 10.1155/2019/4254759
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K_i分别为<0.02 nM, <0.07 nM, 和0.7 nM。Phase 1。	Nature,2019, 10.1038/s41586-019-1472-0 Invest New Drugs,2019, 10.1007/s10637-019-00795-3 Biochem Biophys Res Commun,2019, 511(2):260-265	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.
S5232	Alectinib hydrochloride Alectinib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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