WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 109735
CAS#: 1865733-40-9 (HCl hydrate)
Description: Capmatinib, also known as INCB28060 and INC280, is an orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor INC280 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. Capmatinib was approved in 2020.
MedKoo Cat#: 109735
Name: Capmatinib HCl hydrate
CAS#: 1865733-40-9 (HCl hydrate)
Chemical Formula: C23H21Cl2FN6O2
Molecular Weight: 503.3594
Elemental Analysis: C, 54.88; H, 4.21; Cl, 14.09; F, 3.77; N, 16.70; O, 6.36
Synonym: Capmatinib hydrochloride; NVP-INC 280AAA; INC280; INC-280; INC 280; INCB028060; INCB-028060; INCB 028060; INCB28060; INCB-28060; INCB 28060; Capmatinib.
IUPAC/Chemical Name: 2-Fluoro-N-methyl-4-[7-[(quinolin-6-yl)methyl]imidazo[1,2-b]-[1,2,4]triazin-2-yl]benzamide dihydrochloride hydrate
InChi Key: COWBUPJEEDYWKD-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H17FN6O.2ClH.H2O/c1-25-22(31)18-6-5-16(11-19(18)24)21-13-28-23-27-12-17(30(23)29-21)10-14-4-7-20-15(9-14)3-2-8-26-20;;;/h2-9,11-13H,10H2,1H3,(H,25,31);2*1H;1H2
SMILES Code: O=C(NC)C1=CC=C(C2=NN3C(N=C2)=NC=C3CC4=CC=C5N=CC=CC5=C4)C=C1F.[H]Cl.[H]Cl.[H]O[H]
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >3 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||ATP competitive c-Met kinase inhibitor (IC50=0.13 nM).|
|In vitro activity:||Pancreatic cancer is characterized by a strong stromal reaction. Therefore, the effects of cMET inhibition on ECs and VSMCs were examined. MTT assays in ECs under serum-starved conditions and stimulation with HGF, showed a slight but significant increase in growth that was diminished by INC280 (Capmatinib) (Additional file 3: Figure S3B). No effect upon constitutive conditions was observed (Additional file 3: Figure S3A). EC motility was significantly increased upon incubation with HGF, which was strongly reduced by INC280 (Figure 4A). Regarding activation of signaling pathways, treatment with INC280 strongly inhibited HGF-induced activation of Akt and ERK whereas no effects on constitutive Akt and ERK phosphorylation were found (Figure 4B). Taken together, these results show that INC280 affects ECs only when these cells are stimulated with HGF. Next we analyzed the impact of INC280 on VSMCs. MTT assays showed a dose-dependent inhibition of VSMC growth starting from INC280 (100nM) after 72 hours of incubation (Additional file 3: Figure S3C). In contrast to ECs, stimulation with HGF upon serum-starved conditions had no effect on VSMC growth and, accordingly, INC280 did not have a further growth inhibitory effect in MTT assays (Additional file 3: Figure S3D). Motility upon incubation with HGF in VSMCs was not induced, but targeting cMET with INC280 led to a significant inhibition of constitutive migration (Figure 4C). Finally, Western blotting did not show a substantial effect of INC280 on constitutive Akt phosphorylation and only a minor impact on ERK phosphorylation in VSMCs (Figure 4D). These results indicate that HGF does not affect VSMCs and cMET inhibition with INC280, therefore, has only minor effects on these cells. Reference: BMC Cancer. 2015; 15: 71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340491/|
|In vivo activity:||Tumors underwent a histological examination by a pathologist to determine phenotype and progression. Of the WT mice fed normal diet there were a total of 16 tumors. Twelve of the tumors were papillomas, with one converting to a squamous cell carcinoma (Fig.4d). Three additional tumors were cutaneous lipomas. This is in comparison to Tpl2 −/− mice which had a total of 61 tumors, 51 papillomas, four SCCs, three sebaceous adenomas, and three lipomas. In contrast, no Tpl2 −/− mice fed capmatinib diet had papillomas convert to SCCs (Fig. (Fig.4d).4d). Although Tpl2 −/− mice develop an overall higher tumor burder, there were no statistical differences in tumor size between genotypes and the rate of malignant conversion (7.8 vs. 8.3%) was similar between Tpl2 −/− and WT mice on normal diet. However, the rate of malignant conversion between Tpl2 −/− mice on normal diet (8.3%) vs. Tpl2 −/− mice on Capmatinib diet (0%) was significantly different (p < 0.01). In both genotypes male mice developed more tumors than female mice (Fig.4e; p < 0.05). Reference: Oncogenesis. 2019 Jan; 8(1): 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328619/|
The following data is based on the product molecular weight 503.3594 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Brandes F, Schmidt K, Wagner C, Redekopf J, Schlitt HJ, Geissler EK, Lang SA. Targeting cMET with INC280 impairs tumour growth and improves efficacy of gemcitabine in a pancreatic cancer model. BMC Cancer. 2015 Feb 19;15:71. doi: 10.1186/s12885-015-1064-9. PMID: 25884642; PMCID: PMC4340491.|
|In vivo protocol:||1. Bonan NF, Kowalski D, Kudlac K, Flaherty K, Gwilliam JC, Falkenberg LG, Maradiaga E, DeCicco-Skinner KL. Inhibition of HGF/MET signaling decreases overall tumor burden and blocks malignant conversion in Tpl2-related skin cancer. Oncogenesis. 2019 Jan 10;8(1):1. doi: 10.1038/s41389-018-0109-8. PMID: 30631034; PMCID: PMC6328619.|
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13: Going After METex14 in NSCLC. Cancer Discov. 2019 Aug;9(8):OF9. doi: 10.1158/2159-8290.CD-ND2019-006. Epub 2019 Jun 17. PMID: 31209157.
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16: Li H, Li CW, Li X, Ding Q, Guo L, Liu S, Liu C, Lai CC, Hsu JM, Dong Q, Xia W, Hsu JL, Yamaguchi H, Du Y, Lai YJ, Sun X, Koller PB, Ye Q, Hung MC. MET Inhibitors Promote Liver Tumor Evasion of the Immune Response by Stabilizing PDL1. Gastroenterology. 2019 May;156(6):1849-1861.e13. doi: 10.1053/j.gastro.2019.01.252. Epub 2019 Jan 31. PMID: 30711629; PMCID: PMC6904924.
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