INCB28060

INCB28060 is an orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor INCB28060 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.

Product information

CAS Number: 1029712-80-8

Molecular Weight: 412.42

Formula: C23H17FN6O

Synonym:

INC-280

INC 280

INC280

INCB-028060

INCB 028060

INCB028060

INCB-28060

INCB 28060

INCB28060

Capmatinib

Chemical Name: 2-fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide

Smiles: CNC(=O)C1=CC=C(C=C1F)C1C=NC2=NC=C(CC3=CC4=CC=CN=C4C=C3)N2N=1

InChiKey: LIOLIMKSCNQPLV-UHFFFAOYSA-N

InChi: InChI=1S/C23H17FN6O/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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

INCB28060 inhibits c-MET phosphorylation with an IC50 value of approximately 1 nM and a concentration of approximately 4 nM inhibits c-MET more than 90%. INCB28060 inhibits SNU-5 viability or proliferation with an average IC50 value of 1.2 nM and a calculated IC90 value of 4.6 nM INCB28060 prevents HGF-stimulated H441 cell migration, with IC50 of approximately 2 nM. Again, there is little cell migration at a concentration of 16 nM INCB28060. INCB28060 potently and specifically inhibits c-MET enzyme activity, c-MET-mediated signal transduction, and the c-MET-dependent neoplastic phenotype of tumor cells. INCB28060 exhibits strong antitumor activity in c-MET-dependent tumor models at well-tolerated doses. INCB28060 exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10, 000-fold selectivity over a large panel of human kinases. INCB28060 potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis.

In Vivo:

Oral dosing of INCB28060 results in time- and dose-dependent inhibition of c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models, and the inhibitor is well tolerated at doses that achieve complete tumor inhibition. Furthermore, once daily dosing of 10 mg/kg INCB28060 results in partial regressions in 6 of 10 U-87MG tumor-bearing mice. It is noted that in both S114 and U-87MG models, tumor growth inhibition increases with increased exposure of the compound and that tumor regressions could only be achieved when the compound exposure consistently exceeded 90% of c-MET inhibition. In these studies, INCB28060 is well tolerated at all doses during the treatment periods, with no evidence of overt toxicity or weight loss.

References:

1. Vansteenkiste JF, Van De Kerkhove C, Wauters E, Van Mol P. Capmatinib for the treatment of non-small cell lung cancer. Expert Rev Anticancer Ther. 2019 Aug;19(8):659-671. doi: 10.1080/14737140.2019.1643239. Epub 2019 Aug 1. PMID: 31368815.
2. Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW. Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR- Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Nov 1;36(31):3101-3109. doi: 10.1200/JCO.2018.77.7326. Epub 2018 Aug 29. Erratum in: J Clin Oncol. 2019 Jan 20;37(3):261. PMID: 30156984.
3. Baltschukat S, Engstler BS, Huang A, Hao HX, Tam A, Wang HQ, Liang J, DiMare MT, Bhang HC, Wang Y, Furet P, Sellers WR, Hofmann F, Schoepfer J, Tiedt R. Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation. Clin Cancer Res. 2019 May 15;25(10):3164-3175. doi: 10.1158/1078-0432.CCR-18-2814. Epub 2019 Jan 23. PMID: 30674502.
4. Capmatinib Triggers Responses in NSCLC. Cancer Discov. 2019 Jan;9(1):OF6. doi: 10.1158/2159-8290.CD-NB2018-148. Epub 2018 Nov 14. PMID: 30429129.
5. Esaki T, Hirai F, Makiyama A, Seto T, Bando H, Naito Y, Yoh K, Ishihara K, Kakizume T, Natsume K, Myers A, Doi T. Phase I dose-escalation study of capmatinib (INC280) in Japanese patients with advanced solid tumors. Cancer Sci. 2019 Apr;110(4):1340-1351. doi: 10.1111/cas.13956. Epub 2019 Feb 20. PMID: 30724423; PMCID: PMC6447844.

Products are for research use only. Not for human use.