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INCB28060

Cat. No. M2080
INCB28060 Structure
Synonym:

INC280

Size Price Availability Quantity
10mg USD 98 In stock
50mg USD 300 In stock
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Quality Control
Biological Activity

INCB28060 (also known as INC280) is a potent, orally available selective inhibitor of the c-MET receptor tyrosine kinase, a clinically validated cancer target. 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 blocks c-MET phosphorylation and activation of its key downstream effectors in c-MET-dependent tumor cell lines. INCB28060 potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis in vitro. 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 INCB28060 is well tolerated at doses that achieve complete tumor inhibition.

Protocol
Cell Experiment
Cell lines SUN-5 and SUN-1 cells
Preparation method Optimal cell density used in the viability assay was predetermined for individual cell lines. To determine compound potency, cells were seeded into 96-well microplates at the appropriate density in media containing 1% to 2% FBS and supplemented with serial dilutions of INCB28060 in a final volume of 100 μL per well. After 72-hour incubation, 24 μL of CellTiter 96 AQueous One Solution (Promega) was added to each well, and the plates were incubated for 2 hours in a 37°C incubator. The optical density was measured in the linear range using a microplate reader at 490 nm with wavelength correction at 650 nm. IC50 values were calculated using the GraphPad Prism Software.
Concentrations 0~333 nM
Incubation time 3 days
Animal Experiment
Animal models B16F10 tumour-bearing mice
Formulation 0.5% methylcellulose in saline
Dosages 50mg/kg INCB28060
Administration via oral gavage every day once a day starting from day 2 after tumour injection and twice a day from day 11 until the end of the experiment(2 weeks)
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 412.42
Formula C23H17FN6O
CAS Number 1029712-80-8
Purity 100.00%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Mol Cancer Ther (2017). Figure 4. INCB28060 (Abmole Bioscience. Houston, TX, USA)
Method oral gavage
Cell Lines KPC and orthotopic transplant model mice
Concentrations 1 mg/kg
Incubation Time 7, 14 or 21 days
Results Importantly, the group with dual inhibitor treatment in addition to gemcitabine showed no metastases. This result suggests that the combination of c-Met and Hh inhibitors in addition to gemcitabine has significantly suppressed metastasis formation.
Rating
Source Mol Cancer Ther (2017). Figure 3. INCB28060 (Abmole Bioscience. Houston, TX, USA)
Method oral gavage
Cell Lines KPC and orthotopic transplant model mice
Concentrations 1 mg/kg
Incubation Time 7, 14 or 21 days
Results These results suggest that the resistance to the c-Met and Hh inhibitor is developed following a prolonged treatment of each individual inhibitor; however, the resistance may be overcome by combining both c-Met and Hh inhibitors.
Rating
Source Mol Cancer Ther (2017). Figure 1. INCB28060 (Abmole Bioscience. Houston, TX, USA)
Method oral gavage
Cell Lines KPC and orthotopic transplant model mice
Concentrations 1 mg/kg
Incubation Time 7, 14 or 21 days
Results The data suggest that combination of both inhibitors with gemcitabine shows a trend in shrinkage of primary tumor volume in both mouse models of PDA after one week of treatment regimen.
Rating
Source Can Res (2017). Figure 3.INC280 (Abmole Bioscience).
Method
Cell Lines PDAC cells
Concentrations
Incubation Time
Results As expected, neither the Hh inhibitor nor the HGF/c-Met inhibitor affected the levels of total AnxA2 or P-Y23-AnxA2 in Panc10.05 cells in the singly cultured serum-reduced media (Fig. 3A and B; Supplementary Fig. S5E and S5F). It is likely the concentration of HGFand IGF-1 in serum-reduced media is lower than the effective thresholds.
Rating
Source Nature (2015). Figure 3. PF-04217903 and INCB28060 (AbMole Bioscience)
Method mice treatment in vivo and histological evaluation
Cell Lines B16F10 cells
Concentrations 40mg/kg PF-04217903 and 50mg/kg INCB28060
Incubation Time 2 weeks
Results Systemic treatment of WT mice carrying B16F10 melanomas (which are dependent on MET14) with three different MET tyrosine-kinase inhibitors (PF-04217903, INCB28060 and JNJ-38877605), strongly reduced TAN recruitment .
Rating
Source Nature (2015). Figure 2. PF-04217903 and INCB28060 (AbMole Bioscience)
Method mice treatment in vivo and histological evaluation
Cell Lines B16F10 cells
Concentrations 40mg/kg PF-04217903
Incubation Time 2 weeks
Results "Systemic administration of PF-04217903 decreased the weight and volume of B16F10 melanomas by 36% and 54%, respectively. Instead, MET knockdown in cancer cells only, led to 58% and 75% inhibition of tumour growth and volume.TAN inhibition by PF-04217903 was comparable in both Met-silenced and scrambled B16F10 melanomas."
Rating
Product Citations
References

A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3.
Liu X, et al. Clin Cancer Res. 2011 Nov 15;17(22):7127-38. PMID: 21918175.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: INCB28060, INC280 supplier, c-Met, inhibitors

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