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INCB28060

INCB28060

Catalog No.

A8448

C-Met inhibitor,ATP-competitive and novel

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Grouped product items
Size	Price	Stock
10mM (in 1mL DMSO)	$99.00	In stock
10mg	$85.00	In stock
50mg	$133.00	In stock
100mg	$182.00	In stock

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Background
Product Citation
Chemical Properties
Protocol
Biological Activity
Quality Control

Background

INCB28060, also known as Capmatinib and INC280, is a novel and ATP-competitive inhibitor of c-Met with IC50 of 0.13 nM.

c-Met, also named as hepatocyte growth factor receptor (HGFR) is a receptor tyrosine kinase that is essential for embryonic development and would healing. In many tumor cells, this molecular is overexpressed or mutated and was found to play important roles in tumor cell proliferation, survival, invasion, metastasis and angiogenesis.

In vitro, INCB28060 treatment effectively inhibited activation of c-MET and signaling in cancer cells. As a result, INCB28060 blocked cell proliferation of varying cell lines such as SNU-5 and S114. The cell migration of U-87MG and H441 cells were also highly inhibited1.

The role of c-met was studied using this inhibitor in mouse model. Oral administration of INCB28060 leads to inhibition of c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models. Therefore, INCB28060 has the therapeutic potential in cancer treatment 1.

Reference:
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.

Product Citation

1. Anil Kumar Yadav, et al. "PHA-665752's Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells." Int J Mol Sci. 2024 Mar 1;25(5):2871. PMID: 38474118

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	412.42
Cas No.	1029712-80-8
Formula	C₂₃H₁₇FN₆O
Solubility	insoluble in EtOH; insoluble in H2O; ≥5.15 mg/mL in DMSO with gentle warming
Chemical Name	2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide
SDF	Download SDF
Canonical SMILES	CNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Kinase experiment [1]:
Kinase assays	The assay buffer contained 50 mM Tris-HCl, 10 mM MgCl2, 100 mM NaCl, 0.1 mg/ml BSA, 5mM DTT, pH 7.8. For HTS 0.8 μL of 5 mM of the test compounds dissolved in DMSO were dotted on 384-well plates. To measure IC50s the compound plate was prepared by 3-fold and 11-point serial dilutions. 0.8 μL of the compound in DMSO was transferred from the compound plate to the assay plate. Solutions of 8 nM unphosphorylated c-Met or 0.5 nM phosphorylated c-Met were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide dissolved in DMSO was diluted to 1 μM in assay buffer containing 400 μM ATP (unphosphorylated c-Met) or 160 uM ATP (phosphorylated c-Met). A 20 μL volume of enzyme solution was added to the appropriate wells in each plate and then 20 μL/well of substrate solution to initiate the reaction. The plate was protected from light and incubated at 25 °C for 90 min. The reaction was stopped by adding 20 μL of a solution containing 45 mM EDTA, 50 mM Tris-HCl, 50 mM NaCl, 0.4 mg/ml BSA, 200 nM SA-APC and 3 nM EU-Py20. The plate was incubated for 15-30 min at room temperature and HTRF (homogenous time resolved fluorescence) was measured on a Perkin Elmer Fusion α-FP instrument.
Cell experiment [2]:
Cell lines	Human cancer cell lines (SNU-5, SNU-1, U-87MG, 786-O, A549, H441, H596, H1437, H1993, BT474, A549, and HT-29), MKN-45 cell line, S114 cell line, Blood samples obtained from healthy volunteers and cancer patients
Preparation method	Limited solubility in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	IC50: 0.13 nM (c-MET), 72-hour
Applications	INCB28060 (IC50: 1 nM) inhibited human c-MET phosphorylation and c-MET–mediated signaling in the SNU-5 human gastric cancer cell line. INCB28060 inhibited SNU-5 viability or proliferation with an average IC50 value of 1.2 nM. INCB28060 (2 nM) prevented HGF-stimulated H441 cell migration. INCB28060 exhibited strong antitumor activity in c-MET-dependent tumor models. INCB28060 exhibited picomolar enzymatic potency and was highly specific for c-MET with more than 10,000-fold selectivity over a large panel of human kinases. INCB28060 (24 hours) potently inhibited c-MET-dependent tumor cell proliferation and migration and effectively induced apoptosis.
Animal experiment [2]:
Animal models	Female Balb/c nu/nu mice (Charles River) subcutaneously injected with S114 tumor cells or U-87MG glioblastoma tumor cells
Dosage form	0.03, 0.1, 0.3, 1, 3, or 10 mg/kg
Application	Oral dosing of INCB28060 resulted in time- and dose-dependent inhibition of c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models. INCB28060 was well tolerated at doses that achieve complete tumor inhibition. Once daily dosing of 10 mg/kg INCB28060 resulted in partial regressions in 6 of 10 U-87MG tumor-bearing mice.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Behshad E, Klabe R M, Margulis A, et al. Phosphorylation state-dependent high throughput screening of the c-MET kinase[J]. Current chemical genomics, 2010, 4: 27. [2]. Liu X, Wang Q, Yang G, et al. A novel kinase inhibitor INCB28060 blocks c-MET-dependent signaling, neoplastic activities, and crosstalk with EGFR and HER-3[J]. Clinical Cancer Research, 2011: clincanres. 1157.2011.