Antibodies
EMD 1214063
- 貨號 Cat. No.
- S7067
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
EMD 1214063
Catalog No.S7067
EMD 1214063 is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Phase 1.
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Biological Activity
| Description | EMD 1214063 is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Phase 1. | |||||
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| Targets | c-Met | |||||
| IC50 | 3 nM [1] | |||||
| In vitro | EMD 1214063 inhibits HGF-induced c-Met phosphorylation in A549 cells with IC50 of 6 nM. Treatment with EMD 1214063 induces a marked reduction of c-Met–constitutive phosphorylation in EBC-1 cells with IC50 of 9 nM. EMD 1214063 effectively blocka phosphorylation of the major downstream effectors of the c-Met enzyme, such as Grb2, Gab1, Sos, PLCγ, and phosphoinositide 3-kinase, in EBC-1, MKN-45, and Hs746T cells in the range of 1 to 10 nM. EMD 1214063 considerably inhibits the viability of MKN-45 cells with IC50 of less than 1 nM. Treatment with EMD 1214063 (as low as 0.1 nM) inhibits HGF-induced NCI-H441 cell migration, whereas concentrations of 100 nM to 1 μM almost completely prevents it. [1] | |||||
| In vivo | EMD 1214063 treatment, at doses of 10 mg/kg or more, results in more than 90% inhibition of c-Met phosphorylation in Hs746T xenograft tumor for a period of at least 72 hours. EMD 1214063 induces more than 50% reduction of cyclin D1 expression, which persists after 96 hours upon treatment with doses of 100 mg/kg. A transient induction of p27 and cleaved caspase-3 are also observed upon treatment with EMD 1214063. EMD 1214063 (15 mg/kg, daily) treatment induces complete regression of gastric carcinoma xenografts Hs746T, in which c-Met is amplified, overexpressed, and activated in a ligand-independent fashion. [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| c-Met kinase assay | Kinase inhibition by EMD 1214063 (1 and 10μM) is assessed in vitro using a panel of 242 different kinases. Biochemical activity is measured in a flash-plate assay. His6-tagged recombinant human c-Met kinase domain (Aa 974–end; 20 ng) and biotinylated poly-Ala-Glu-Lys-Tyr (6:2:5:1; 500 ng) are incubated with or without the test compound for 90 minutes at room temperature in 100 μL buffer containing 0.3 μCi33P-ATP, 2.5 μg polyethylene glycol 20.000, and 1% dimethyl sulfoxide (DMSO). Radioactivity is measured with a TopCount microplate scintillation and luminescence counter. |
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Animal Study: [1]
| Animal Models | Human gastric carcinoma xenografts Hs746T |
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| Dosages | 15 mg/kg |
| Administration | daily |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01014936 | Recruiting | Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available | EMD Serono | 2009-11 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 492.57 |
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| Formula | C29H28N6O2 |
| CAS No. | 1100598-32-0 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | mg/mL (<1 mM) |
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| Water | mg/mL (<1 mM) | ||
| Ethanol | mg/mL (<1 mM) | ||
| * <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 | Benzonitrile, 3-[1,6-dihydro-1-[[3-[5-[(1-methyl-4-piperidinyl)methoxy]-2-pyrimidinyl]phenyl]methyl]-6-oxo-3-pyridazinyl]- |
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