- 貨號 Cat. No.
- S2788
- 規格 Size
- 10mgã€50mg
- 品牌 Brand
- Selleckchem
Description
INCB28060
Catalog No.S2788
INCB28060 is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM, inactive against RONβ, as well as EGFR and HER-3. Phase 1.
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10mg |
USD 214 |
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50mg |
USD 718 |
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
Description |
INCB28060 is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM, inactive against RONβ, as well as EGFR and HER-3. Phase 1. |
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Targets |
c-MET |
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IC50 |
0.13 nM [1] |
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In vitro |
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 inhibits human c-MET phosphorylation and c-MET-mediated signaling in cancer cells. INCB28060 inhibits c-MET-dependent cell proliferation and survival, and prevents anchorage-independent cancer cell growth and cell migration. [1] |
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In vivo |
INCB28060 shows strong antitumor activity in c-MET-dependent mouse tumor models, even oral treatment of 0.03 mg/kg INCB28060 causes approximately 50% inhibition of c-MET-phosphorylation. Dose-dependent inhibition of tumor growth is observed in tumor-bearing mice. [1] |
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Features |
Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family). |
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Protocol(Only for Reference)
Kinase Assay: [1]
c-Met Kinase Assay |
The assay buffer contains 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 INCB28060 dissolved in DMSO are dotted on 384-well plates. DMSO titration suggests that the maximum tolerated concentration of the solvent is 4%. To measure IC50s the INCB28060 plate is prepared by 3-fold and 11-point serial dilutions. 0.8 μL of INCB28060 in DMSO is transferred from INCB28060 plate to the assay plate. The final concentration of DMSO is 2%. Solutions of 8 nM unphosphorylated c-Met or 0.5 nM phosphorylated c-Met are prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide dissolved in DMSO is 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 (or assay buffer for the enzyme blank) is added to the appropriate wells in each plate and then 20 μL/well of substrate solution to initiate the reaction. The plate is protected from light and incubated at 25 °C for 90 minutes. The reaction is 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 EUPy20. The plate is incubated for 15-30 minutes at room temperature and HTRF (homogenous time resolved fluorescence) is measured on a Perkin Elmer Fusion α-FP instrument. The HTRF program settings used are as follows: Primary excitation filter 330/30, Primary window: 200 uSec, Primary delay: 50 uSec, Number of flashes: 15, Well read time: 2000 |
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Cell Assay: [1]
Cell lines |
H441 cells |
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Concentrations |
0.24, 1, 4, 16, 63 nM |
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Incubation Time |
24 hours |
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Method |
H441 cells are seeded in RPMI-1640 medium containing 10% FBS and grown to complete confluence. Gaps are introduced by scraping cells with a P200 pipette tip. Cells are then stimulated with 50 ng/mL recombinant human HGF to induce migration across the gap in the presence of various concentrations of INCB28060. After an overnight incubation, representative photographs are taken and a semiqualitative assessment of inhibition of cell migration is conducted. |
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Animal Study: [1]
Animal Models |
Eight-week-old female Balb/c nu/nu mice (Charles River) are inoculated subcutaneously with 4 × 106 tumor cells (S114 model) or with 5 × 106 tumor cells (U-87MG glioblastoma model). |
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Dosages |
3, 10, 30 mg/kg |
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Administration |
INCB28060 is orally dosed, twice each day. |
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Solubility |
1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL |
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1
References
Clinical Trial Information( data from http://clinicaltrials.gov)
NCT Number |
Recruitment |
Conditions |
Sponsor
/Collaborators |
Start Date |
Phases |
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NCT01072266 |
Completed |
Advanced Malignancies |
Incyte Corporation|Novartis Pharmaceuticals |
2010-01 |
Phase 1 |
Download INCB28060 SDF
Molecular Weight (MW) |
412.42 |
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Formula |
C23H17FN6O
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CAS No. |
1029712-80-8 |
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Storage |
3 years -20℃Powder |
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6 months-80℃in DMSO |
Syonnyms |
N/A |
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Solubility (25°C) * |
In vitro |
DMSO |
2 mg/mL (4 mM) |
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Water |
<1 mg/mL (<1 mM) |
Ethanol |
<1 mg/mL (<1 mM) |
In vivo |
1% DMSO/30% polyethylene glycol/1% Tween 80, |
30 mg/mL |
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
Chemical Name |
2-fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide |
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