Antibodies
AMG-208
- 貨號 Cat. No.
- S1316
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
AMG-208
Catalog No.S1316
AMG 208 is a highly selective c-Met inhibitor with IC50 of 9 nM. Phase 1.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | AMG 208 is a highly selective c-Met inhibitor with IC50 of 9 nM. Phase 1. | |||||
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| Targets | c-Met | |||||
| IC50 | 9 nM [1] | |||||
| In vitro | 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. [1] 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. [1] 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. [2]AMG-208 is identified to be a c-MET and RON dual selective inhibitor. [3] | |||||
| 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, Vssof 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. [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| In Vitro Kinase Assay | IC50 measurements versus c-Met kinase and its mutants are determined using homogenous time-resolved fluorescence (HTRF) assays. AMG-208 is tested in a 10-point dose-response curve for each enzyme using an ATP concentration of two-thirds Km for each. Most assays consists of enzyme mixed with kinase reaction buffer [20 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 5 mM MnCl2, 100 mM NaCl, 1.5 mM EGTA]. A final concentration of 1 mM DTT, 0.2 mM NaVO4, and 20 μg/mL BSA is added before each assay. For all assays, 5.75 mg/mL streptavidin-allophycocyanin and 0.1125 nM Eu-PT66 are added immediately before the HTRF reaction. Plates are incubated for 30 minutes at room temperature and read on a Discovery instrument Molecules are tested in a 10-point serial dilution for each c-Met construct using an ATP concentration of two thirds Km value that is determined for each enzyme preparation and calculated using the Eadie-Hofstee and Lineweaver-Burke methods. |
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Animal Study: [1]
| Animal Models | Male Sprague-Dawley rats |
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| Dosages | ≤2 mg/kg |
| Administration | Administered via i.v. and p.o. |
| Solubility | 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00813384 | Active, not recruiting | Cancer|Oncology|Tumors|Advanced Malignancy|Advanced Solid Tumors|Oncology Patients | Amgen | 2008-12 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 383.4 |
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| Formula | C22H17N5O2 |
| CAS No. | 1002304-34-8 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 0.25 mg/mL (<1 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 | 7-methoxy-4-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)quinoline |
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