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INCB28060

In stock
Catalog No.
A8448
C-Met inhibitor,ATP-competitive and novel
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$66.00
In stock
10mg
$98.00
In stock
50mg
$315.00
In stock
100mg
$525.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

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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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt412.42
Cas No.1029712-80-8
FormulaC23H17FN6O
Solubility≥5.15mg/mL in DMSO with gentle warming
Chemical Name2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide
SDFDownload SDF
Canonical SMILESCNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

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.

Biological Activity

Description INCB28060 is a novel, ATP-competitive inhibitor of c-MET with an IC50 value of 0.13 nM.
Targets c-MET          
IC50 0.13 nM          

Quality Control

Quality Control & MSDS

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Chemical structure

INCB28060