1029712-80-8 Usage
MET small molecule inhibitor
Capmatinib(Synonyms: INC280; INCB28060) is a competitive inhibitor with very potent and selective activity against MET compared to other kinases. It has been shown in vitro that cell lines made resistant to erlotinib, an EGFR inhibitor, could be resensitized after capmatinib treatment. Results from a phase Ib/II study of patients with EGFR-mutated, MET-dysregulated NSCLC have shown promising responses to a combination of capmatinib and gefitinib (EGFR TKI) following disease progression from an only EGFR TKI treatment regimen. Recommended phase II dose was determined to be capmatinib 400 mg twice/day and gefitinib 250 mg once/day. Most common adverse events were nausea, peripheral edema, decreased appetite, rash, and increased amylase and lipase levels.
Originator
Novartis
Description
Different sources of media describe the Description of 1029712-80-8 differently. You can refer to the following data:
1. INCB 28060 is an inhibitor of heptatocyte growth factor receptor (HGFR, also known as c-Met), potently blocking in vitro kinase activity (IC50 = 0.13 nM) as well as constitutive or HGF-stimulated activity in cells (IC50 values range from 0.3 to 1.1 nM). It blocks cell proliferation and migration or induces apoptosis in different types of cancer cells. INCB 28060 is orally bioavailable and inhibits the growth of HGFR-dependent tumors in mice. It also improves efficacy of gemcitabine in a mouse pancreatic cancer model and reduces migration and adhesion in ovarian cancer cell models.
2. Capmatinib is a competitive inhibitor with very potent and selective activity against MET compared to other kinases.
Uses
2-Fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide is used in the preparation of a combination formulation with allosteric SHP2 inhibitor TNO155. Used in treatment of non-small cell lung cancer with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping).
Side effects
Most common adverse events were nausea, peripheral edema, decreased appetite, rash, and increased amylase and lipase levels.
in vitro
It has been shown in vitro that cell lines made resistant to erlotinib, an EGFR inhibitor, could be resensitized after capmatinib treatment. Results from a phase Ib/II study of patients with EGFR-mutated, MET-dysregulated NSCLC have shown promising responses to a combination of capmatinib and gefitinib (EGFR TKI) following disease progression from an only EGFR TKI treatment regimen. Recommended phase II dose was determined to be capmatinib 400 mg twice/day and gefitinib 250 mg once/day.
references
1. liu x, wang q, yang g, et al. a novel kinase inhibitor, incb28060, blocks c-met-dependent signaling, neoplastic activities, and cross-talk with egfr and her-3. clinical cancer research : an official journal of the american association for cancer research. 2011;17(22):7127-7138.
Check Digit Verification of cas no
The CAS Registry Mumber 1029712-80-8 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,2,9,7,1 and 2 respectively; the second part has 2 digits, 8 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1029712-80:
(9*1)+(8*0)+(7*2)+(6*9)+(5*7)+(4*1)+(3*2)+(2*8)+(1*0)=138
138 % 10 = 8
So 1029712-80-8 is a valid CAS Registry Number.
1029712-80-8Relevant articles and documents
Absorption, distribution, metabolism, and excretion of capmatinib (inc280) in healthy male volunteers and in vitro aldehyde oxidase phenotyping of the major metabolite
Glaenzel, Ulrike,Jin, Yi,Hansen, Regine,Schroer, Kirsten,Rahmanzadeh, Gholamreza,Pfaar, Ulrike,Van Lier, Jan Jaap,Borell, Hubert,Meissner, Axel,Camenisch, Gian,Zhao, Sylvia
, p. 873 - 885 (2020)
Capmatinib (INC280), a highly selective and potent inhibitor of the MET receptor tyrosine kinase, has demonstrated clinically meaningful efficacy and a manageable safety profile in patients with advanced non-small-cell lung cancer harboring MET exon 14-skipping mutations. We investigated the absorption, distribution, metabolism, and excretion of capmatinib in six healthy male volunteers after a single peroral dose of 600 mg 14C-labeled capmatinib. The mass balance, blood and plasma radioactivity, and plasma capmatinib concentrations were determined along with metabolite profiles in plasma, urine, and feces. The metabolite structures were elucidated using mass spectrometry and comparing with reference compounds. The parent compound accounted for most of the radioactivity in plasma (42.9% 6 2.9%). The extent of oral absorption was estimated to be 49.6%; the Cmax of capmatinib in plasma was reached at 2 hours (median time to reach Cmax). The apparent mean elimination half-life of capmatinib in plasma was 7.84 hours. Apparent distribution volume of capmatinib during the terminal phase was moderate-to-high (geometric mean 473 l). Metabolic reactions involved lactam formation, hydroxylation, N-dealkylation, formation of a carboxylic acid, hydrogenation, N-oxygenation, glucuronidation, and combinations thereof. M16, the most abundant metabolite in plasma, urine, and feces was formed by lactam formation. Absorbed capmatinib was eliminated mainly by metabolism and subsequent biliary/fecal and renal excretion. Excretion of radioactivity was complete after 7 days. CYP phenotyping demonstrated that CYP3A was the major cytochrome P450 enzyme subfamily involved in hepatic microsomal metabolism, and in vitro studies in hepatic cytosol indicated that M16 formation was mainly catalyzed by aldehyde oxidase.
Preparation method of capmatinib
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Paragraph 00433-0044, (2020/11/09)
The invention provides a preparation method of capmatinib. The inventor carries out wide and deep research, massive screening and testing. A compound represented by a formula III is adopted as the rawmaterial for hydrolysis reaction and methylation reaction to obtain a formula I compound, namely capmatinib. The method is mild in reaction condition, environment-friendly, low in energy consumption,good in product purity and high in yield, and is suitable for industrial large-scale production.
IMIDAZOTRIAZINES AND IMIDAZOPYRIMIDINES AS KINASE INHIBITORS
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Page/Page column 45, (2008/12/05)
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