1029712-80-8 Usage
Description
INCB28060, also known as 2-Fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide, is a potent inhibitor of the hepatocyte growth factor receptor (HGFR or c-Met). It effectively blocks in vitro kinase activity, as well as constitutive or HGF-stimulated activity in cells, with IC50 values ranging from 0.13 to 1.1 nM. INCB28060 is orally bioavailable and has demonstrated the ability to inhibit the growth of HGFR-dependent tumors in mice. Additionally, it has shown improved efficacy when combined with gemcitabine in a mouse pancreatic cancer model and has been effective in reducing migration and adhesion in ovarian cancer cell models.
Uses
Used in Pharmaceutical Industry:
INCB28060 is used as an inhibitor of the hepatocyte growth factor receptor (HGFR or c-Met) for its potent blocking of in vitro kinase activity and its ability to inhibit the growth of HGFR-dependent tumors in mice. This makes it a promising candidate for the development of targeted cancer therapies.
Used in Combination Therapies:
INCB28060 is used in the preparation of a combination formulation with allosteric SHP2 inhibitor TNO155 for the treatment of non-small cell lung cancer with specific mutations, such as those that lead to mesenchymal-epithelial transition or MET exon 14 skipping. The combination therapy aims to enhance the efficacy of treatment and overcome resistance in cancer patients.
Used in Cancer Treatment:
INCB28060 is used as an anticancer agent for its ability to block cell proliferation and migration or induce apoptosis in different types of cancer cells. Its oral bioavailability and effectiveness in mouse models make it a potential candidate for the development of new cancer treatments.
Used in Drug Delivery Systems:
To improve the delivery, bioavailability, and therapeutic outcomes of INCB28060, novel drug delivery systems are being developed. These systems aim to enhance the efficacy of the compound against cancer cells by employing various organic and metallic nanoparticles as carriers for INCB28060 delivery.
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
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 0034-0035; 0038-0039, (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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