product name AMG-208
Description: AMG 208 is a highly potent and selective small-molecule inhibitor of c-Met with IC50 of 9 nM. AMG 208 inhibits the ligand-dependent and ligand-independent activation of c-Met, inhibiting its tyrosine kinase activity, which may result in cell growth inhibition in tumors that overexpress c-Met. C-Met encodes the hepatocyte growth factor receptor tyrosine kinase, plays an important role in epithelial cell proliferation and has been shown to be overexpressed in a variety of cancers.
References: J Med Chem. 2008 May 22;51(10):2879-82; Bioorg Med Chem Lett. 2009 Nov 15;19(22):6307-12.
383.4
Formula
C22H17N5O2
CAS No.
1002304-34-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 0.25 mg/mL (0.65 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402768
| In Vitro |
In vitro activity: AMG-208 shows the potent inhibition of kinase c-Met activity with IC50 of 9 nM in a cell-free assay. Besides, AMG-208 treatment also leads to the inhibition of HGF-mediated c-Met phosphorylation in PC3 cells with IC50 of 46 nM. Incubation of AMG-208 with rat and human liver microsomes in the presence of NADPH qualitatively yields C6-phenylarene oxidation products as the major metabolites. Pre-incubation of AMG-208 with human liver microsomes for 30 minutes shows a potent time-dependent inhibition for CYP3A4 metabolic activity with IC50 of 4.1 μM, which is an eightfold decrease relative to the IC50 (32 μM) without preincubation. AMG-208 is identified to be a c-MET and RON dual selective inhibitor. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In male Sprague−Dawley rats, AMG-208 (0.5 mg/kg i.v.) shows a high bioavailability with Cl of 0.37 L/h/kg, Vss of 0.38 L/kg and T1/2 of 1 hour, while AMG-208 (2 mg/kg i.v.) shows a bioavailability with AUC0→∞ of 2517 ng·h/mL and F of 43%, respectively. |
| Animal model | Male Sprague-Dawley rats |
| Formulation & Dosage | Dissolved in DMSO; ≤2 mg/kg; i.v. or p.o. |
| References | J Med Chem. 2008 May 22;51(10):2879-82; Bioorg Med Chem Lett. 2009 Nov 15;19(22):6307-12. |
Tenofovir (Disoproxil Fumarate)
Related Posts
product name AMG-208
Description: AMG 208 is a highly potent and selective small-molecule inhibitor of c-Met with IC50 of 9 nM. AMG 208 inhibits the ligand-dependent and ligand-independent activation of c-Met, inhibiting its tyrosine kinase activity, which may result in cell growth inhibition in tumors that overexpress c-Met. C-Met encodes the hepatocyte growth factor receptor tyrosine kinase, plays an important role in epithelial cell proliferation and has been shown to be overexpressed in a variety of cancers.
References: J Med Chem. 2008 May 22;51(10):2879-82; Bioorg Med Chem Lett. 2009 Nov 15;19(22):6307-12.
383.4
Formula
C22H17N5O2
CAS No.
1002304-34-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 0.25 mg/mL (0.65 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402768
| In Vitro |
In vitro activity: AMG-208 shows the potent inhibition of kinase c-Met activity with IC50 of 9 nM in a cell-free assay. Besides, AMG-208 treatment also leads to the inhibition of HGF-mediated c-Met phosphorylation in PC3 cells with IC50 of 46 nM. Incubation of AMG-208 with rat and human liver microsomes in the presence of NADPH qualitatively yields C6-phenylarene oxidation products as the major metabolites. Pre-incubation of AMG-208 with human liver microsomes for 30 minutes shows a potent time-dependent inhibition for CYP3A4 metabolic activity with IC50 of 4.1 μM, which is an eightfold decrease relative to the IC50 (32 μM) without preincubation. AMG-208 is identified to be a c-MET and RON dual selective inhibitor. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In male Sprague−Dawley rats, AMG-208 (0.5 mg/kg i.v.) shows a high bioavailability with Cl of 0.37 L/h/kg, Vss of 0.38 L/kg and T1/2 of 1 hour, while AMG-208 (2 mg/kg i.v.) shows a bioavailability with AUC0→∞ of 2517 ng·h/mL and F of 43%, respectively. |
| Animal model | Male Sprague-Dawley rats |
| Formulation & Dosage | Dissolved in DMSO; ≤2 mg/kg; i.v. or p.o. |
| References | J Med Chem. 2008 May 22;51(10):2879-82; Bioorg Med Chem Lett. 2009 Nov 15;19(22):6307-12. |
Tenofovir (Disoproxil Fumarate)