c-Met

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
S1068	Crizotinib (PF-02341066)	<1 mg/mL	9 mg/mL	<1 mg/mL
S1119	Cabozantinib (XL184, BMS-907351)	<1 mg/mL	100 mg/mL	<1 mg/mL
S1111	Foretinib (GSK1363089)	<1 mg/mL	100 mg/mL	<1 mg/mL
S1070	PHA-665752	<1 mg/mL	128 mg/mL	<1 mg/mL
S1080	SU11274	<1 mg/mL	92 mg/mL	2 mg/mL
S7674	Savolitinib(AZD6094, HMPL-504)	<1 mg/mL	16 mg/mL	<1 mg/mL
S3759	Norcantharidin	-1 mg/mL	33 mg/mL	-1 mg/mL
S1112	SGX-523	<1 mg/mL	3 mg/mL	<1 mg/mL
S1561	BMS-777607	<1 mg/mL	47 mg/mL	<1 mg/mL
S2753	Tivantinib (ARQ 197)	<1 mg/mL	73 mg/mL	<1 mg/mL
S1114	JNJ-38877605	<1 mg/mL	37 mg/mL	<1 mg/mL
S1094	PF-04217903	<1 mg/mL	5 mg/mL	<1 mg/mL
S1361	Glesatinib (MGCD265)	<1 mg/mL	104 mg/mL	<1 mg/mL
S2788	Capmatinib (INCB28060)	<1 mg/mL	2 mg/mL	<1 mg/mL
S1124	BMS-754807	<1 mg/mL	92 mg/mL	92 mg/mL
S2201	BMS-794833	<1 mg/mL	94 mg/mL	<1 mg/mL
S1316	AMG-208	<1 mg/mL	0.25 mg/mL	<1 mg/mL
S2774	MK-2461	<1 mg/mL	99 mg/mL	<1 mg/mL
S2859	Golvatinib (E7050)	<1 mg/mL	20 mg/mL	<1 mg/mL
S2747	AMG-458	<1 mg/mL	21 mg/mL	<1 mg/mL
S2761	NVP-BVU972	<1 mg/mL	68 mg/mL	68 mg/mL
S7067	Tepotinib (EMD 1214063)	<1 mg/mL	5 mg/mL	<1 mg/mL
S8167	AMG 337	<1 mg/mL	95 mg/mL	95 mg/mL
S7014	Merestinib (LY2801653)	<1 mg/mL	100 mg/mL	100 mg/mL
S8404	S49076	<1 mg/mL	87 mg/mL	<1 mg/mL
S7669	NPS-1034	<1 mg/mL	100 mg/mL	4 mg/mL

c-Met抑制剂（26）
新c-Met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。	Nature, 2012, 487(7408):505-9 Nat Med, 2011, 17(9):1116-20 Nat Med, 2012, 18(6):883-91	(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).
S1119	Cabozantinib (XL184, BMS-907351) Cabozantinib (XL184, BMS-907351)是一种有效的VEGFR2抑制剂，在无细胞试验中IC50为0.035 nM，也能有效抑制c-Met、 Ret、 Kit、Flt-1/3/4、Tie2和AXL，IC50分别为1.3 nM，4 nM，4.6 nM，12 nM/11.3 nM/6 nM，14.3 nM 和 7 nM。	Cancer Discov, 2014, 4(7):816-27 Nat Commun, 2014, 5:3116 Cancer Res, 2016, 76(8):2094-104	Effects of AXL inhibitors on induction of pAKT and rescue of pERK following AXL overexpression. R428, 500 nmol/L; XL184, 3 umol/L; XL880, 100 nmol/L; in the presence or absence of 2 umol/L PLX4720. shAXL is a positive control.
S1111	Foretinib (GSK1363089) Foretinib (GSK1363089)是一种ATP竞争性的HGFR和VEGFR抑制剂，对Met和KDR作用最强，在无细胞试验中IC50分别为0.4 nM和0.9 nM。对Ron， Flt-1/3/4， Kit， PDGFRα/β和Tie-2作用效果稍弱，对FGFR1和EGFR几乎没有抑制活性。Phase 2。	Nat Genet, 2012, 44(8):852-60 Clin Cancer Res, 2015, 21(10):2379-87 Leukemia, 2014, 28(3):629-41	D. Effects of erlotinib and inhibitors of PI3K, MEK, MET or IGF-1R on phosphorylation of AKT and ERK in ER3 cells.
S1070	PHA-665752 PHA-665752是一种有效的，选择性的，ATP竞争性c-Met抑制剂，在无细胞试验中IC50为9 nM，对c-Met的选择性比对 RTKs和 STKs高50倍以上。	Nat Genet, 2012, 44(8):852-60 Cancer Discov, 2013, 3(12):1404-15 Cell Res, 2015, 10.1038/cr.2015.16	A, representative Western blot analyses of samples obtained from NSCLC cells exposed to 1 umol/L erlotinib or PHA-665,752 for 6 hours. Levels of total and phosphorylated forms of EGFR, MET, and HER3. B, representative Western blot analyses of samples obtained as described in A showing the levels of EGFR downstream signaling mediators. Protein samples obtained from untreated and treated cells were separated by SDS-PAGE and immunoblotted with each antibody. Tubulin served to ensure equal loading.
S1080	SU11274 SU11274是一种选择性Met抑制剂，在无细胞试验中IC50为10 nM，对PGDFRβ，EGFR和Tie2没有作用。	Nat Med, 2012, 18(7):1118-22 Clin Cancer Res, 2014, 20(22):5796-807 Biomaterials, 2016, 78:129-39	Inhibition of c-MET sensitizes PTEN deficient tumor cells to EGFR TKI-induced apoptosis. PTEN deficient TGFα-EGFR^WT;InkΔ2/3-/-;PTEN^lox GBM tumor cells were treated with gefitinib (10 uM) and/or the c-MET kinase inhibitor SU11274 (10 uM). Immunoblot analysis of total cell lysates from TGFα-EGFR^WT;InkΔ2/3-/-;PTEN^lox GBM tumor cells treated with the indicated inhibitors using c-MET and c-MET phosphotyrosine 1234,1235 antibodies. Anti β-tubulin probing is used as an internal loading control.
S7674^New	Savolitinib(AZD6094, HMPL-504) Savolitinib (volitinib, AZD6094, HMPL-504)是新型的、有效的、选择性的MET抑制剂，在对多种病例迹象中进行临床研发，如乳头状肾细胞癌。其对c-Met和p-Met的IC50分别为5 nM和3 nM。相对于所检测的274种激酶，Savolitinib对c-Met具有精确的选择性。
S3759^New	Norcantharidin Norcantharidin is a synthetic anticancer compound which is a dual inhibitor for c-Met and EGFR in human colon cancers.
S1112	SGX-523 SGX-523是一种选择性的Met抑制剂，IC50为4 nM，对BRAFV599E， c-Raf， Abl和p38α无抑制活性。Phase 1。	Am J Respir Crit Care Med, 2016, 10.1164/rccm.201509-1878OC J Hepatol, 2014, 60(1):143-51 Clin Cancer Res, 2013, 19(9):2584-91
S1561	BMS-777607 BMS-777607是一种Met相关的抑制剂，作用于c-Met，Axl，Ron和Tyro3，在无细胞试验中IC50分别为3.9 nM，1.1 nM，1.8 nM和4.3 nM，作用于Met相关靶点比作用于Lck， VEGFR-2，和TrkA/B选择性高40倍，比作用于其他受体和非受体激酶选择性高500多倍。Phase 1/2。	J Clin Invest, 2014, 124(11):4737-52 J Pathol, 2015, 237(1):14-24 J Med Chem, 2015,	Numbers of clonogenic cells from L3.6pl cells and CSCs^＋24/44/ESAin duplicate were counted. Clonogenic growth from the cell control was set as 100%.
S2753	Tivantinib (ARQ 197) Tivantinib (ARQ 197)是第一个非ATP竞争性的c-Met抑制剂，在无细胞试验中K_i为0.355 μM，对Ron几乎没有作用活性，对EGFR， InsR， PDGFRα和FGFR1/4没有抑制作用。Phase 3。	Clin Cancer Res, 2017, pii: clincanres.3118.2016 J Exp Clin Cancer Res, 2015, 34:118 Cell Signal, 2013, 25(12):2652-60	Effect of tivantinib on the mitotic index was compared with the antimitotic drugs paclitaxel and vinblastine after overnight treatment of the HLE cell line with two different concentrations of each drug
S1114	JNJ-38877605 JNJ-38877605是一种ATP竞争性的c-Met抑制剂，IC50为4 nM，作用于c-Met比作用于200种其他酪氨酸和丝-苏氨酸激酶选择性高600倍。Phase 1。	Nature, 2015, 10.1038/nature14407 Gut, 2014, 10.1136/gutjnl-2013-305257 Clin Cancer Res, 2017, 10.1158/1078-0432.CCR-16-3118	Inducers of EMT. (A) Expression of Hgf, Egf, and Tgfb1 genes in RETAAD tumors analyzed by qRT-PCR. Hgf and Tgfb1 are preferentially expressed in PMN-MDSC, while Egf is preferentially expressed in tumor cells. Data are from four individual experiments using sorted fractions of PMNMDSC and melanoma cells. Bars represent mean 6 SD. (B) NBT-II cells (100 cells per well) were plated for 4 d to allow for colony growth and were pretreated for 24 h with inhibitors before the addition of PMN-MDSC. After co-culture with PMN-MDSCs in the presence of inhibitors, cells were fixed and stained with anti-rat desmoplakin. Green, Desmoplakin; red, H2b (nuclear stain). PD153035-EGFR inhibitor, JNJ38877605-c-met (HGFR) inhibitor, and SB525334-TGF-bR1 inhibitor. Images are representative of three independent experiments.
S1094	PF-04217903 PF-04217903是一种选择性的，ATP竞争性c-Met抑制剂，在A549细胞中IC50为4.8 nM，对致癌基因突变型敏感(对Y1230C突变型没有活性)。Phase 1。	J Clin Invest, 2016, 126(6):2181-90 Clin Cancer Res, 2014, 20(17):4559-73 Clin Cancer Res, 2015, 21(1):166-74	(A) p-MET, p-eIF4E, and p-ERK1/2 levels in S462 cells 24 hours after treatment with 1 μM PF04217903 and 750 nM PD901. (B) Change in cell number after treatment with 1 μM PF04217903 (PF903) and/or 750 nM PD901. Graph represents the average log2 of fold change in cell number 72 hours after treatment relative to time 0 (mean ± SD, n = 3).
S1361	Glesatinib (MGCD265) Glesatinib (MGCD265)是一种有效的，多靶点，及ATP竞争性的c-Met和VEGFR1/2/3抑制剂，IC50分别为1 nM， 3 nM/3 nM/4 nM，也抑制Ron和Tie2。Phase 1/2。	Cancer Lett, 2013, 340(1):43-50 Int J Clin Exp Pathol, 2013, 6(10):2082-91	c-MET/RON inhibitors restore sensitivity to lapatinib in SK-BR-3-LR cells. The concentration used was 0.1 uM for crizotinib, MGCD-265, XL880, sunitinib, dasatinib, TAE-684, and RON inhibitor I. Columns, means; bars, SEMs (n = 3). The phosphorylation of HER2, AKT and ERK1/2 was determined by Western blotting.
S2788	Capmatinib (INCB28060) Capmatinib (INCB28060)是一种新型的，ATP竞争性c-MET抑制剂，无细胞试验中IC50为0.13 nM，对RONβ，EGFR和HER-3无活性。Phase 1。	Dev Cell, 2014, 29(4):421-36 Oncogenesis, 2017, 6(4):e307 PLoS One, 2016, 11(3):e0150507	(a) MTS assay for the treatment of selected MET-subclones (2+3) and EMT-subclones (4+10) with the MET-inhibitor capmatinib. The cell lines are listed as they appear in the figure. All absorbance values were normalized to the absorbance for the control samples of the individual cell line. EMT- and MET-subclones responded significantly different to capmatinib treatment at 8 nm (P<0.0121).
S1124	BMS-754807 BMS-754807是一种有效的IGF-1R/InsR可逆性抑制剂，在无细胞试验中IC50为1.8 nM/1.7 nM，对Met，Aurora A/B，TrkA/B和Ron作用稍弱，对Flt3， Lck，MK2，PKA，PKC等几乎没有抑制活性。Phase 2。	Clin Cancer Res, 2013, 19(11):2984-94 Cancer Res, 2014, 74(20):5866-77 Mol Cell Biol, 2015, 35(7):1182-96
S2201	BMS-794833 BMS-794833是一种有效的，ATP竞争性Met/VEGFR2抑制剂，IC50为1.7 nM/15 nM，也抑制Ron， Axl和Flt3，IC50低于3 nM；是BMS-817378的前体药物。 Phase 1。
S1316	AMG-208 AMG-208是一种高度选择性的c-Met抑制剂，IC50为9 nM。Phase 1。
S2774	MK-2461 MK-2461是一种有效的，多靶点抑制剂，作用于c-Met(WT/mutants)，IC50为0.4-2.5 nM，对Ron，和Flt1作用效果稍弱；作用于c-Met比作用于FGFR1， FGFR2， FGFR3， PDGFRβ， KDR， Flt3， Flt4， TrkA和TrkB选择性高8到30倍。Phase 1/2。		Both V-H cells and V-J cells are treated with MK-2461, XL-184 or ABT-869, respectively. (i-k) Western blot analysis of sFlt-1 expression after incubation with three VEGF-A receptor inhibitors or in the control.
S2859	Golvatinib (E7050) Golvatinib (E7050)是c-Met和VEGFR-2双重抑制剂，IC50分别为14 nM和16 nM，不抑制bFGF刺激的HUVEC生长(浓度高达1000 nM)。Phase 1/2。	Cancer Sci, 2017, 108(7):1378-1385	PC-9/LMC-GR cells (2 × 105 cells/well) were incubated in 6-well plates with various concentrations of gefitinib with or without crizotinib (1 μmol/L) or golvatinib (1 μmol/L) for 1 hour. Cell lysate were obtained and subjected to immunoblotting with antibodies toward the indicated molecules.
S2747	AMG-458 AMG-458是一种有效的c-Met抑制剂，K_i为1.2 nM，作用于c-Met比作用于VEGFR2选择性高350倍左右。
S2761	NVP-BVU972 NVP-BVU972是一种有效的，选择性的Met抑制剂，IC50为14 nM。
S7067	Tepotinib (EMD 1214063) Tepotinib (EMD 1214063)是一种有效的，选择性的c-Met抑制剂，IC50为4 nM，作用于c-Met比作用于IRAK4， TrkA， Axl， IRAK1和Mer选择性高200倍以上。Phase 1。	Cell Res, 2015, 10.1038/cr.2015.16 J Virol, 2016, 90(14):6412-29	Ectopic expression of a RNAi-resistant SMARCE1 cDNA resensitizes SMARCE1-knockdown cells to MET inhibition in MET-amplified NSCLC cells. The above-described cells were grown in the absence or presence of 300 nM Crizotinib, 150 nM EMD1214063, or 150 nM PHA665752. Cells were then fixed, stained and photographed after 12 days (untreated) or 28 days (treated).
S8167	AMG 337 AMG 337是一种口服的、ATP竞争性的、高度选择性MET 受体抑制剂。IC50为1 nM。
S7014	Merestinib (LY2801653) LY2801653是一种2型ATP竞争型的慢抑制剂，抑制MET酪氨酸激酶，Ki值为2 nM。药效的停留时间为0.00132 min(-1)，t_^1/2为525 min。
S8404	S49076 S49076是一种新型的、有效的MET, AXL/MER和FGFR1/2/3抑制剂，IC50低于20 nM。
S7669	NPS-1034 NPS-1034是一种双Met/Axl抑制剂，IC50分别为48 nM和10.3 nM。

研究领域

产品类型

c-Met

信号通路图

研究领域