Capmatinib hydrochloride
- Product Name
- Capmatinib hydrochloride
- CAS No.
- 1865733-40-9
- Chemical Name
- Capmatinib hydrochloride
- Synonyms
- INC-280 2HCl.H2O;INCB28060 2HCl.H2O;NVP-INC280 2HCl.H2O;Capmatinib 2HCl.H2O;Capmatinib hydrochloride;Capmatinib hydrochloride Hydrate;Capmatinib HCl hydrate (INCB-28060;Capmatinib dihydrochloride hydrate;Capmatinib Hydrochloride Hydrate （INCB28060）;2-fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide dihydrochloride monohydrate
- CBNumber
- CB04848242
- Molecular Formula
- C23H20ClFN6O2
- Formula Weight
- 466.9
- MOL File
- 1865733-40-9.mol
Capmatinib hydrochloride Property
- InChIKey
- XCHIKTXPDQTRMI-UHFFFAOYSA-N
- SMILES
- C(C1C=CC2N=CC=CC=2C=1)C1=CN=C2N=CC(C3C=CC(C(=O)NC)=C(F)C=3)=NN12.Cl.O
Capmatinib hydrochloride Chemical Properties,Usage,Production
Description
Capmatinib dihydrochloride hydrate is a orally active,reversible MET tyrosine kinase inhibitor that received approval for advanced non-small cell lung cancer(NSCLC) harboring MET exon 14 skipping mutationa. Capmatinib dihydrochloride hydrate can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. Capmatinib dihydrochloride hydrate potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib dihydrochloride hydrate is largely metabolized by CYP3A4 and aldehyde oxidase[1-3].
Origin
Capmatinib was first reported in 2011 by Liu et al., who showed that in both in vivo and in vitro mice studies using human cell lines, capmatinib had a 10,000-fold selectivity for c-met over a large panel of human kinase. They showed that capmatinib can block the c-MET phosphorylation and activation of downstream targets, including HGF. They further showed that activated c-met upregulates cancer-promoting EGFR and HER-3 pathways. Baltschukat et al. further investigated capmatinib in NSCLC[4].
Mechanism of action
Tabrecta (capmatinib) is a kinase inhibitor that targets MET, including the mutant variant produced by exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that reduces its negative regulation, leading to increased downstream MET signaling.
Toxicity evaluation
Effects During Pregnancy and Lactation No information is available on the clinical use of capmatinib during breastfeeding. Because capmatinib is 96% bound to plasma proteins, the amount in milk is likely to be low. The manufacturer recommends that breastfeeding be discontinued during capmatinib therapy and for 1 week after the last dose.
References
[1] HSUROBERT NagasakaMisako BenjaminDavid J. The Development and Role of Capmatinib in the Treatment of MET-Dysregulated Non-Small Cell Lung Cancer-A Narrative Review.[J]. Cancers, 2023. DOI:10.3390/cancers15143561.
[2] LIUXIANGDONG. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3.[J]. Clinical Cancer Research, 2011. DOI:10.1158/1078-0432.CCR-11-1157.
[3] BALTSCHUKATSABRINA. Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation.[J]. Clinical Cancer Research, 2019. DOI:10.1158/1078-0432.CCR-18-2814.
[4] HsuRobert, NagasakaMisako, BenjaminDavid J. "The Development and Role of Capmatinib in the Treatment of MET-Dysregulated Non-Small Cell Lung Cancer-A Narrative Review." Cancers 15 14 (2023).
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View Lastest Price from Capmatinib hydrochloride manufacturers
- Product
- Capmatinib hydrochloride Hydrate 1865733-40-9
- Price
- US $0.00-0.00/kg
- Min. Order
- 1kg
- Purity
- ＞99% by HPLC
- Supply Ability
- 10kg/month
- Release date
- 2023-07-22
- Product
- Capmatinib hydrochloride 1865733-40-9
- Price
- US $1.00-0.50/kg
- Min. Order
- 1kg
- Purity
- 99%
- Supply Ability
- 200kg
- Release date
- 2023-12-11