Target General Infomation
Target ID
T40474 (Former ID: TTDC00110)
Target Name
Proto-oncogene c-Met (MET)
Synonyms
Tyrosine-protein kinase Met; Scatter factor receptor; SF receptor; Met proto-oncogene tyrosine kinase; Hepatocyte growth factor receptor; HGF/SF receptor; HGF-SF receptor; HGF receptor; C-met; C-Met receptor tyrosine kinase
Gene Name
MET
Target Type
Successful target
[1]
Disease [+] 2 Target-related Diseases +
1 Lung cancer [ICD-11: 2C25]
2 Thyroid cancer [ICD-11: 2D10]
Function
Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.
BioChemical Class
Kinase
UniProt ID
MET_HUMAN
EC Number
EC 2.7.10.1
Sequence
MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEH
HIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMAL
VVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPE
FRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECIL
TEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS
AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEF
TTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFL
LDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW
CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKK
TRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVIT
SISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF
AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVH
EAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPV
FKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL
LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQ
IKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGS
CRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHF
NEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVL
SLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKF
VHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKF
TTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCW
HPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVD
TRPASFWETS
Drugs and Modes of Action
Approved Drug(s) [+] 2 Approved Drugs +
1 Cabozantinib Drug Info Approved Thyroid cancer [2], [3]
2 Crizotinib Drug Info Approved Non-small-cell lung cancer [4], [5]
Clinical Trial Drug(s) [+] 37 Clinical Trial Drugs +
1 Beperminogene perplasmid Drug Info Phase 3 Heart disease [6]
2 RG3638 Drug Info Phase 3 Non-small-cell lung cancer [7]
3 Savolitinib Drug Info Phase 3 Renal cell carcinoma [8]
4 Tivantinib Drug Info Phase 3 Solid tumour/cancer [9], [10]
5 AMG 208 Drug Info Phase 2 Solid tumour/cancer [11]
6 AMG 337 Drug Info Phase 2 Solid tumour/cancer [12]
7 CMX-2043 Drug Info Phase 2 Myocardial reperfusion injury [13]
8 EMD-1214063 Drug Info Phase 2 Hepatocellular carcinoma [8]
9 Emibetuzumab Drug Info Phase 2 Solid tumour/cancer [14]
10 HM-5016504 Drug Info Phase 2 Solid tumour/cancer [15]
11 INCB28060 Drug Info Phase 2 Hepatocellular carcinoma [16]
12 LY-2875358 Drug Info Phase 2 Solid tumour/cancer [17]
13 LY2801653 Drug Info Phase 2 Solid tumour/cancer [18]
14 SAR-125844 Drug Info Phase 2 Solid tumour/cancer [19]
15 Volitinib Drug Info Phase 2 Solid tumour/cancer [15]
16 XL880 Drug Info Phase 2 Squamous head and neck cell carcinom [20], [21]
17 Anti-C-met CAR-T cells Drug Info Phase 1/2 Colorectal cancer [22]
18 ChronSeal Drug Info Phase 1/2 Fibrosis [23]
19 MGCD516 Drug Info Phase 1/2 Solid tumour/cancer [8]
20 MK-2461 Drug Info Phase 1/2 Alzheimer disease [24]
21 MSC2156119 Drug Info Phase 1/2 Solid tumour/cancer [25]
22 Sym015 Drug Info Phase 1/2 Solid tumour/cancer [8], [14]
23 ABBV-399 Drug Info Phase 1 Solid tumour/cancer [26]
24 ABT-700 Drug Info Phase 1 Advanced solid tumour [27]
25 Altiratinib Drug Info Phase 1 Solid tumour/cancer [28]
26 Autologous T Cells Expressing MET scFv CAR Drug Info Phase 1 Melanoma [29]
27 C-Met/PD-L1 CAR-T Cell Drug Info Phase 1 Hepatocellular carcinoma [30]
28 CBT-101 Drug Info Phase 1 Solid tumour/cancer [8]
29 E-7050 Drug Info Phase 1 Head and neck cancer [31], [32]
30 EMD-1204831 Drug Info Phase 1 Solid tumour/cancer [33]
31 Hepapoietin Drug Info Phase 1 Liver disease [34]
32 JNJ-38877605 Drug Info Phase 1 Solid tumour/cancer [35]
33 LY3164530 Drug Info Phase 1 Advanced cancer [36]
34 Merestinib, LY2801653 Drug Info Phase 1 Solid tumour/cancer [37]
35 MK-8033 Drug Info Phase 1 Solid tumour/cancer [38]
36 PF-4217903 Drug Info Phase 1 Solid tumour/cancer [39]
37 SGX523 Drug Info Phase 1 Solid tumour/cancer [40], [41]
Preclinical Drug(s) [+] 1 Preclinical Drugs +
1 Mteron-F1 Drug Info Preclinical Mucositis [42]
Mode of Action [+] 5 Modes of Action +
Inhibitor [+] 43 Inhibitor drugs +
1 Cabozantinib Drug Info [3], [43]
2 Savolitinib Drug Info [8]
3 Tivantinib Drug Info [9]
4 Emibetuzumab Drug Info [14]
5 HM-5016504 Drug Info [45]
6 SAR-125844 Drug Info [55]
7 BMS-777607 Drug Info [58]
8 ChronSeal Drug Info [59]
9 MGCD516 Drug Info [60]
10 MK-2461 Drug Info [24]
11 MSC2156119 Drug Info [61]
12 Sym015 Drug Info [8]
13 ABBV-399 Drug Info [14]
14 Altiratinib Drug Info [43], [63]
15 CBT-101 Drug Info [8]
16 EMD-1204831 Drug Info [65]
17 Hepapoietin Drug Info [66]
18 JNJ-38877605 Drug Info [67]
19 MK-8033 Drug Info [70]
20 PF-4217903 Drug Info [71]
21 SGX523 Drug Info [72]
22 1-(2-nitrophenethyl)-1H-pyrrolo[3,2-b]pyridine Drug Info [73]
23 1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine Drug Info [73]
24 1-benzyl-1H-pyrrolo[3,2-b]pyridine Drug Info [73]
25 3-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine Drug Info [73]
26 AM7 Drug Info [74]
27 Anti-cMET mab Drug Info [45]
28 APS-3010 Drug Info [45]
29 BAY-85-3474 Drug Info [45]
30 BMS-536924 Drug Info [75]
31 C-Met kinase inhibitors Drug Info [45]
32 CMET Avimer polypeptides Drug Info [45]
33 DP-3590 Drug Info [45]
34 MG-516 Drug Info [45]
35 PF-00614435 Drug Info [45]
36 PHA-665752 Drug Info [45]
37 PMID21123062C27 Drug Info [77]
38 PMID21967808CR-16 Drug Info [78]
39 PMID24210504C1o Drug Info [79]
40 PRS-110 Drug Info [45]
41 RP-1040 Drug Info [45]
42 SU11274 Drug Info [80]
43 TP-801 Drug Info [45]
Modulator [+] 16 Modulator drugs +
1 Crizotinib Drug Info [1]
2 Beperminogene perplasmid Drug Info [44]
3 RG3638 Drug Info [45]
4 AMG 208 Drug Info [46]
5 AMG 337 Drug Info [47]
6 CMX-2043 Drug Info [48]
7 EMD-1214063 Drug Info [49]
8 INCB28060 Drug Info [50]
9 LY2801653 Drug Info [53], [54]
10 Volitinib Drug Info [56]
11 XL880 Drug Info [57]
12 ABT-700 Drug Info [62]
13 E-7050 Drug Info [64]
14 LY3164530 Drug Info [68]
15 Merestinib, LY2801653 Drug Info [69]
16 GE-137 Drug Info [76]
CAR-T-Cell-Therapy [+] 2 CAR-T-Cell-Therapy drugs +
1 Anti-C-met CAR-T cells Drug Info [22]
2 Autologous T Cells Expressing MET scFv CAR Drug Info [29]
CAR-T-Cell-Therapy(Dual specific) [+] 1 CAR-T-Cell-Therapy(Dual specific) drugs +
1 C-Met/PD-L1 CAR-T Cell Drug Info [30]
Stimulator [+] 1 Stimulator drugs +
1 Mteron-F1 Drug Info [42]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Affiliated Biological Pathways
KEGG Pathway [+] 18 KEGG Pathways +
1 Ras signaling pathway
2 Rap1 signaling pathway
3 Cytokine-cytokine receptor interaction
4 Endocytosis
5 PI3K-Akt signaling pathway
6 Axon guidance
7 Focal adhesion
8 Adherens junction
9 Bacterial invasion of epithelial cells
10 Epithelial cell signaling in Helicobacter pylori infection
11 Malaria
12 Pathways in cancer
13 Transcriptional misregulation in cancer
14 Proteoglycans in cancer
15 MicroRNAs in cancer
16 Renal cell carcinoma
17 Melanoma
18 Central carbon metabolism in cancer
PID Pathway [+] 10 PID Pathways +
1 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
2 Arf6 signaling events
3 Signaling events mediated by TCPTP
4 Posttranslational regulation of adherens junction stability and dissassembly
5 Direct p53 effectors
6 Syndecan-1-mediated signaling events
7 Stabilization and expansion of the E-cadherin adherens junction
8 a6b1 and a6b4 Integrin signaling
9 FGF signaling pathway
10 Regulation of retinoblastoma protein
Reactome [+] 1 Reactome Pathways +
1 Sema4D mediated inhibition of cell attachment and migration
WikiPathways [+] 10 WikiPathways +
1 TGF beta Signaling Pathway
2 Signaling of Hepatocyte Growth Factor Receptor
3 Focal Adhesion
4 Extracellular vesicle-mediated signaling in recipient cells
5 Signaling Pathways in Glioblastoma
6 miR-targeted genes in squamous cell - TarBase
7 miR-targeted genes in muscle cell - TarBase
8 miR-targeted genes in lymphocytes - TarBase
9 miR-targeted genes in epithelium - TarBase
10 Semaphorin interactions
Target-Related Models and Studies
Target Validation
References
REF 1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5887).
REF 3 Clinical pipeline report, company report or official report of Exelixis (2011).
REF 4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4903).
REF 5 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
REF 6 ClinicalTrials.gov (NCT02144610) Safety and Efficacy of Subjects With Critical Limb Ischemia. U.S. National Institutes of Health.
REF 7 ClinicalTrials.gov (NCT02488330) An Extension Study of Onartuzumab in Patients With Solid Tumors on Study Treatment Previously Enrolled in a Company Sponsored Study.
REF 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 9 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7948).
REF 10 A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second- or third-line therapy in the patients with metastatic gastric cancer. Invest New Drugs. 2014 Apr;32(2):355-61.
REF 11 ClinicalTrials.gov (NCT02420587) AMG 208 Tumor Microenvironment in Metastatic Castration Resistant Prostate Cancer (mCRPC). U.S. National Institutes of Health.
REF 12 ClinicalTrials.gov (NCT02016534) Phase 2 Study of AMG 337 in MET Amplified Gastric/Esophageal Adenocarcinoma or Other Solid Tumors. U.S. National Institutes of Health.
REF 13 ClinicalTrials.gov (NCT02103959) Safety and Efficacy of CMX-2043 for Protection of the Heart and Kidneys in Subjects Undergoing Coronary Angiography. U.S. National Institutes of Health.
REF 14 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 15 ClinicalTrials.gov (NCT02127710) A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC). U.S. National Institutes of Health.
REF 16 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031741)
REF 17 ClinicalTrials.gov (NCT01900652) A Study of LY2875358 in Non Small Cell Lung Cancer (NSCLC) Participants. U.S. National Institutes of Health.
REF 18 ClinicalTrials.gov (NCT01285037) A Study of LY2801653 in Advanced Cancer. U.S. National Institutes of Health.
REF 19 ClinicalTrials.gov (NCT02435121) A Study Assessing Efficacy and Safety of SAR125844 in NSCLC Patients With MET Amplification. U.S. National Institutes of Health.
REF 20 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5679).
REF 21 Clinical pipeline report, company report or official report of Exelixis (2011).
REF 22 ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
REF 23 ClinicalTrials.gov (NCT00797706) Phase I/II Dose Ranging CHRONSEAL Study in Venous Leg Ulcers. U.S. National Institutes of Health.
REF 24 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
REF 25 ClinicalTrials.gov (NCT01982955) MSC2156119J With Gefitinib in Subjects With Advanced Non-small Cell Lung Cancer. U.S. National Institutes of Health.
REF 26 ClinicalTrials.gov (NCT02099058) A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors. U.S. National Institutes of Health.
REF 27 ClinicalTrials.gov (NCT01472016) Study of ABT-700 in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health.
REF 28 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040094)
REF 29 ClinicalTrials.gov (NCT03060356) Autologous T Cells Expressing MET scFv CAR (RNA CART-cMET)
REF 30 ClinicalTrials.gov (NCT03672305) Clinical Study on the Efficacy and Safety of c-Met/PD-L1 CAR-T Cell Injection in the Treatment of HCC
REF 31 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7956).
REF 32 ClinicalTrials.gov (NCT02533102) Pharmacokinetics and Food Effect of Single Oral Dose of E7050 in Healthy Volunteers.
REF 33 ClinicalTrials.gov (NCT01110083) First-in-Man, Dose-escalation Trial of c-Met Kinase Inhibitor EMD 1204831 in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health.
REF 34 Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease. Aliment Pharmacol Ther. 2002 Feb;16(2):235-42.
REF 35 ClinicalTrials.gov (NCT00651365) A Safety and Dose-finding Study of JNJ-38877605 in Patients With Advanced or Refractory Solid Tumors.. U.S. National Institutes of Health.
REF 36 ClinicalTrials.gov (NCT02221882) A Study of LY3164530 in Participants With Cancer
REF 37 Clinical pipeline report, company report or official report of Eli Lilly.
REF 38 ClinicalTrials.gov (NCT00559182) A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001). U.S. National Institutes of Health.
REF 39 ClinicalTrials.gov (NCT00706355) A Study of PF-04217903 in Patients With Advanced Cancer. U.S. National Institutes of Health.
REF 40 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5709).
REF 41 ClinicalTrials.gov (NCT00607399) Safety Study of SGX523, a Small Molecule Met Inhibitor, to Treat Solid Tumors. U.S. National Institutes of Health.
REF 42 Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22.
REF 43 Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
REF 44 Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
REF 45 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1815).
REF 46 A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors. Oncotarget. 2015 Jul 30;6(21):18693-706.
REF 47 J Clin Oncol 32:5s, 2014 (suppl; abstr 2508).
REF 48 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 49 EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors. Clin Cancer Res. 2013 Jun 1;19(11):2941-51.
REF 50 National Cancer Institute Drug Dictionary (drug id 666907).
REF 51 Clinical pipeline report, company report or official report of Eli Lilly.
REF 52 LY2875358, a neutralizing and internalizing anti-MET bivalent antibody, inhibits HGF-dependent and HGF-independent MET activation and tumor growth. Clin Cancer Res. 2014 Dec 1;20(23):6059-70.
REF 53 Clinical pipeline report, company report or official report of Eli Lilly.
REF 54 LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2013 Aug;31(4):833-44.
REF 55 The selective intravenous inhibitor of the MET tyrosine kinase SAR125844 inhibits tumor growth in MET-amplified cancer. Mol Cancer Ther. 2015 Feb;14(2):384-94.
REF 56 Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
REF 57 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
REF 58 Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607... J Med Chem. 2009 Mar 12;52(5):1251-4.
REF 59 Clinical pipeline report, company report or official report of Kringle Pharma.
REF 60 Role and relevance of TrkB mutations and expression in non-small cell lung cancer. Clin Cancer Res. 2011 May 1;17(9):2638-45.
REF 61 Identification and optimization of pyridazinones as potent and selective c-Met kinase inhibitors. Bioorg Med Chem Lett. 2015 Apr 1;25(7):1597-602.
REF 62 J Clin Oncol 32:5s, 2014 (suppl; abstr 2507).
REF 63 Clinical pipeline report, company report or official report of Deciphera Pharmaceuticals.
REF 64 E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5.
REF 65 2012 ASCO Annual Meeting.
REF 66 Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease. Alimentary Pharmacology & Therapeutics Volume 16, Issue 2, pages 235-242, February 2002.
REF 67 The c-Met Tyrosine Kinase Inhibitor JNJ-38877605 Causes Renal Toxicity through Species-Specific Insoluble Metabolite Formation. Clin Cancer Res. 2015 May 15;21(10):2297-304.
REF 68 Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
REF 69 The c-Met inhibitors: a new class of drugs in the battle against advanced nonsmall-cell lung cancer. Curr Pharm Des. 2012;18(37):6155-68.
REF 70 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
REF 71 Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012 Apr;11(4):1036-47.
REF 72 CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
REF 73 Discovery of 4-azaindoles as novel inhibitors of c-Met kinase. Bioorg Med Chem Lett. 2009 May 15;19(10):2780-4.
REF 74 c-Met inhibitors with novel binding mode show activity against several hereditary papillary renal cell carcinoma-related mutations. J Biol Chem. 2008 Feb 1;283(5):2675-83.
REF 75 Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
REF 76 Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nat Med. 2015 Aug;21(8):955-61.
REF 77 Fused bicyclic derivatives of 2,4-diaminopyrimidine as c-Met inhibitors. Bioorg Med Chem Lett. 2011 Jan 1;21(1):164-7.
REF 78 Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group. Bioorg Med Chem. 2011 Nov 1;19(21):6274-84.
REF 79 Design and synthesis of novel 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine derivatives as selective G-protein-coupled receptor kinase-2 and -5 inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6711-6.
REF 80 Potent and selective inhibitors of the Met [hepatocyte growth factor/scatter factor (HGF/SF) receptor] tyrosine kinase block HGF/SF-induced tumor cell growth and invasion. Mol Cancer Ther. 2003 Nov;2(11):1085-92.

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