c-Met
Signaling Pathway Map
Research Area
- Inhibitory Selectivity
- Solubility
| Catalog No. | Product Name | Solubility(25°C) | ||
|---|---|---|---|---|
| Water | DMSO | Alcohol | ||
| 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 |
| S7564 | SAR125844 | ˂1 mg/mL | 11 mg/mL | ˂1 mg/mL |
| S9308 | Pulsatilla saponin D | -1 mg/mL | 100 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 | MGCD-265 analog | <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 |
| S3759 | Norcantharidin | -1 mg/mL | 33 mg/mL | -1 mg/mL |
| S7669 | NPS-1034 | <1 mg/mL | 100 mg/mL | 4 mg/mL |
| S7674 | Savolitinib(AZD6094, HMPL-504) | <1 mg/mL | 16 mg/mL | <1 mg/mL |
c-Met Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1068 |
Crizotinib (PF-02341066)Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. |
(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) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. |
Level of phospho-proteins in RTK and PI3K/Akt/mTOR pathways in treated tumors, detected with western blot. (c) Phospho-Erk and phospho-S6 intensity in MDSCs when co-transfected with ERK2 and p70S6K, detected with western blot.
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| S1111 |
Foretinib (GSK1363089)Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2. |
D. Effects of erlotinib and inhibitors of PI3K, MEK, MET or IGF-1R on phosphorylation of AKT and ERK in ER3 cells.
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| S1070 |
PHA-665752PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs. |
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.
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|
| S1080 |
SU11274SU11274 is a selective Met inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2. |
Inhibition of c-MET sensitizes PTEN deficient tumor cells to EGFR TKI-induced apoptosis. PTEN deficient TGFα-EGFRWT;InkΔ2/3-/-;PTENlox 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-EGFRWT;InkΔ2/3-/-;PTENlox 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.
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| S7564New |
SAR125844SAR125844 is a potent intravenously active and highly selective MET kinase inhibitor, displaying nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and H1094Y, Y1235D, M1250T, L1195V, and D1228H kinase domain mutants (IC50 values of 0.22, 1.7, 6.5, 65, and 81 nmol/L, respectively). |
||
| S9308New |
Pulsatilla saponin DPulsatilla saponin D, isolated from the root of Pulsatilla koreana, targets c-Met and exerts antiangiogenic and antitumor activities. |
||
| S1112 |
SGX-523SGX-523 is a selective Met inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α. Phase 1. |
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|
| S1561 |
BMS-777607BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2. |
IHC for phospho-Neu Y1248 in tumors, 1 hour after lapatinib treatment (day 1, d1), and day 7 (d7), 1 hour after final treatment with BMS-777607. Representative images are shown.
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| S2753 |
Tivantinib (ARQ 197)Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki of 0.355 μM in a cell-free assay, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. Phase 3. |
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-38877605JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM, 600-fold selective for c-Met than 200 other tyrosine and serine-threonine kinases. Phase 1. |
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-04217903PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM in A549 cell line, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1. |
(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).
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| S1361 |
MGCD-265 analogMGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively; also inhibits Ron and Tie2. Phase 1/2. |
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.
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| S2788 |
Capmatinib (INCB28060)Capmatinib (INCB28060) is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM in a cell-free assay, inactive against RONβ, as well as EGFR and HER-3. Phase 1. |
Western blots of MET and Akt for parental, crizotinib-resistant, or capmatinib-resistant cells treated for 4 hours with a range of doses of capmatinib, crizotinib, or glesatinib (G-I).
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| S1124 |
BMS-754807BMS-754807 is a potent and reversible inhibitor of IGF-1R/InsR with IC50 of 1.8 nM/1.7 nM in cell-free assays, less potent to Met, Aurora A/B, TrkA/B and Ron, and shows little activity to Flt3, Lck, MK2, PKA, PKC etc. Phase 2. |
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| S2201 |
BMS-794833BMS-794833 is a potent ATP competitive inhibitor of Met/VEGFR2 with IC50 of 1.7 nM/15 nM, also inhibits Ron, Axl and Flt3 with IC50 of <3 nM; a prodrug of BMS-817378. Phase 1. |
||
| S1316 |
AMG-208AMG 208 is a highly selective c-Met inhibitor with IC50 of 9 nM. Phase 1. |
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| S2774 |
MK-2461MK-2461 is a potent, multi-targeted inhibitor for c-Met(WT/mutants) with IC50 of 0.4-2.5 nM, less potent to Ron, Flt1; 8- to 30-fold greater selectivity of c-Met targets versus FGFR1, FGFR2, FGFR3, PDGFRβ, KDR, Flt3, Flt4, TrkA, and TrkB. 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.
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| S2859 |
Golvatinib (E7050)Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2. |
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.
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| S2747 |
AMG-458AMG 458 is a potent c-Met inhibitor with Ki of 1.2 nM, ~350-fold selectivity for c-Met than VEGFR2 in cells. |
||
| S2761 |
NVP-BVU972NVP-BVU972 is a selective and potent Met inhibitor with IC50 of 14 nM. |
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| S7067 |
Tepotinib (EMD 1214063)Tepotinib (EMD 1214063) is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Phase 1. |
-S706701Z0220150917.gif)
-S706701Z0220150917.gif)
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).
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| S8167 |
AMG 337AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor with an IC50 of 1 nM. |
||
| S7014 |
Merestinib (LY2801653)LY2801653 is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM, a pharmacodynamic residence time (Koff) of 0.00132 min(-1) and t1/2 of 525 min. |
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| S8404 |
S49076S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 values below 20 nmol/L. |
||
| S3759 |
NorcantharidinNorcantharidin is a synthetic anticancer compound which is a dual inhibitor for c-Met and EGFR in human colon cancers. |
||
| S7669 |
NPS-1034NPS-1034 is a dual Met/Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively. |
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| S7674 |
Savolitinib(AZD6094, HMPL-504)Savolitinib (volitinib, AZD6094, HMPL-504) is a novel, potent, and selective MET inhibitor currently in clinical development in various indications, including PRCC. The IC50 values of this compound for c-Met and p-Met are 5 nM and 3 nM, respectively. It shows exquisite selectivity for c-Met over 274 kinase. |
-TAE684(NVP-TAE684)-Dacomitinib-Clin-Cancer-Res-20150808.gif)
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1068 |
Crizotinib (PF-02341066)Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. |
(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) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. |
Level of phospho-proteins in RTK and PI3K/Akt/mTOR pathways in treated tumors, detected with western blot. (c) Phospho-Erk and phospho-S6 intensity in MDSCs when co-transfected with ERK2 and p70S6K, detected with western blot.
|
|
| S1111 |
Foretinib (GSK1363089)Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2. |
D. Effects of erlotinib and inhibitors of PI3K, MEK, MET or IGF-1R on phosphorylation of AKT and ERK in ER3 cells.
|
|
| S1070 |
PHA-665752PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs. |
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 |
SU11274SU11274 is a selective Met inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2. |
Inhibition of c-MET sensitizes PTEN deficient tumor cells to EGFR TKI-induced apoptosis. PTEN deficient TGFα-EGFRWT;InkΔ2/3-/-;PTENlox 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-EGFRWT;InkΔ2/3-/-;PTENlox 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.
|
|
| S7564New |
SAR125844SAR125844 is a potent intravenously active and highly selective MET kinase inhibitor, displaying nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and H1094Y, Y1235D, M1250T, L1195V, and D1228H kinase domain mutants (IC50 values of 0.22, 1.7, 6.5, 65, and 81 nmol/L, respectively). |
||
| S9308New |
Pulsatilla saponin DPulsatilla saponin D, isolated from the root of Pulsatilla koreana, targets c-Met and exerts antiangiogenic and antitumor activities. |
||
| S1112 |
SGX-523SGX-523 is a selective Met inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α. Phase 1. |
|
|
| S1561 |
BMS-777607BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2. |
IHC for phospho-Neu Y1248 in tumors, 1 hour after lapatinib treatment (day 1, d1), and day 7 (d7), 1 hour after final treatment with BMS-777607. Representative images are shown.
|
|
| S2753 |
Tivantinib (ARQ 197)Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki of 0.355 μM in a cell-free assay, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. Phase 3. |
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-38877605JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM, 600-fold selective for c-Met than 200 other tyrosine and serine-threonine kinases. Phase 1. |
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-04217903PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM in A549 cell line, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1. |
(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 |
MGCD-265 analogMGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively; also inhibits Ron and Tie2. Phase 1/2. |
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) is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM in a cell-free assay, inactive against RONβ, as well as EGFR and HER-3. Phase 1. |
Western blots of MET and Akt for parental, crizotinib-resistant, or capmatinib-resistant cells treated for 4 hours with a range of doses of capmatinib, crizotinib, or glesatinib (G-I).
|
|
| S1124 |
BMS-754807BMS-754807 is a potent and reversible inhibitor of IGF-1R/InsR with IC50 of 1.8 nM/1.7 nM in cell-free assays, less potent to Met, Aurora A/B, TrkA/B and Ron, and shows little activity to Flt3, Lck, MK2, PKA, PKC etc. Phase 2. |
|
|
| S2201 |
BMS-794833BMS-794833 is a potent ATP competitive inhibitor of Met/VEGFR2 with IC50 of 1.7 nM/15 nM, also inhibits Ron, Axl and Flt3 with IC50 of <3 nM; a prodrug of BMS-817378. Phase 1. |
||
| S1316 |
AMG-208AMG 208 is a highly selective c-Met inhibitor with IC50 of 9 nM. Phase 1. |
||
| S2774 |
MK-2461MK-2461 is a potent, multi-targeted inhibitor for c-Met(WT/mutants) with IC50 of 0.4-2.5 nM, less potent to Ron, Flt1; 8- to 30-fold greater selectivity of c-Met targets versus FGFR1, FGFR2, FGFR3, PDGFRβ, KDR, Flt3, Flt4, TrkA, and TrkB. 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) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2. |
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-458AMG 458 is a potent c-Met inhibitor with Ki of 1.2 nM, ~350-fold selectivity for c-Met than VEGFR2 in cells. |
||
| S2761 |
NVP-BVU972NVP-BVU972 is a selective and potent Met inhibitor with IC50 of 14 nM. |
||
| S7067 |
Tepotinib (EMD 1214063)Tepotinib (EMD 1214063) is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Phase 1. |
-S706701Z0220150917.gif)
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 337AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor with an IC50 of 1 nM. |
||
| S7014 |
Merestinib (LY2801653)LY2801653 is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM, a pharmacodynamic residence time (Koff) of 0.00132 min(-1) and t1/2 of 525 min. |
||
| S8404 |
S49076S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 values below 20 nmol/L. |
||
| S3759 |
NorcantharidinNorcantharidin is a synthetic anticancer compound which is a dual inhibitor for c-Met and EGFR in human colon cancers. |
||
| S7669 |
NPS-1034NPS-1034 is a dual Met/Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively. |
||
| S7674 |
Savolitinib(AZD6094, HMPL-504)Savolitinib (volitinib, AZD6094, HMPL-504) is a novel, potent, and selective MET inhibitor currently in clinical development in various indications, including PRCC. The IC50 values of this compound for c-Met and p-Met are 5 nM and 3 nM, respectively. It shows exquisite selectivity for c-Met over 274 kinase. |
-TAE684(NVP-TAE684)-Dacomitinib-Clin-Cancer-Res-20150808.gif)
