WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205898
CAS#: 913376-83-7
Description: AMG 458 is a potent c-Met inhibitor with Ki of 1 nM ~ 2.0 nM. AMG-458 was found to significantly inhibit tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight.
MedKoo Cat#: 205898
Name: AMG-458
CAS#: 913376-83-7
Chemical Formula: C30H29N5O5
Exact Mass: 539.21687
Molecular Weight: 539.58176
Elemental Analysis: C, 66.78; H, 5.42; N, 12.98; O, 14.83
AMG-458, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.
Synonym: AMG458; AMG-458; AMG 458
IUPAC/Chemical Name: 1-(2-hydroxy-2-methylpropyl)-N-(5-((7-methoxyquinolin-4-yl)oxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide
InChi Key: GLBZSOQDAOLMGC-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H29N5O5/c1-19-27(29(37)35(20-8-6-5-7-9-20)34(19)18-30(2,3)38)28(36)33-26-13-11-22(17-32-26)40-25-14-15-31-24-16-21(39-4)10-12-23(24)25/h5-17,38H,18H2,1-4H3,(H,32,33,36)
SMILES Code: O=C(C1=C(C)N(CC(C)(O)C)N(C2=CC=CC=C2)C1=O)NC3=NC=C(OC4=CC=NC5=CC(OC)=CC=C45)C=C3
The following data is based on the product molecular weight 539.58176 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Li B, Torossian A, Sun Y, Du R, Dicker AP, Lu B. Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e525-31. doi: 10.1016/j.ijrobp.2012.06.025. Epub 2012 Jul 24. PubMed PMID: 22836051.
2: Liu L, Norman MH, Lee M, Xi N, Siegmund A, Boezio AA, Booker S, Choquette D, D'Angelo ND, Germain J, Yang K, Yang Y, Zhang Y, Bellon SF, Whittington DA, Harmange JC, Dominguez C, Kim TS, Dussault I. Structure-based design of novel class II c-Met inhibitors: 2. SAR and kinase selectivity profiles of the pyrazolone series. J Med Chem. 2012 Mar 8;55(5):1868-97. Epub 2012 Feb 24. PubMed PMID: 22320327.
3: Tiedt R, Degenkolbe E, Furet P, Appleton BA, Wagner S, Schoepfer J, Buck E, Ruddy DA, Monahan JE, Jones MD, Blank J, Haasen D, Drueckes P, Wartmann M, McCarthy C, Sellers WR, Hofmann F. A drug resistance screen using a selective MET inhibitor reveals a spectrum of mutations that partially overlap with activating mutations found in cancer patients. Cancer Res. 2011 Aug 1;71(15):5255-64. Epub 2011 Jun 22. PubMed PMID: 21697284.
4: Foti RS, Rock DA, Wienkers LC, Wahlstrom JL. Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos. 2010 Jun;38(6):981-7. Epub 2010 Mar 4. PubMed PMID: 20203109.
5: Teffera Y, Colletti AE, Harmange JC, Hollis LS, Albrecht BK, Boezio AA, Liu J, Zhao Z. Chemical reactivity of methoxy 4-o-aryl quinolines: identification of glutathione displacement products in vitro and in vivo. Chem Res Toxicol. 2008 Nov;21(11):2216-22. PubMed PMID: 18837519.
6: Liu L, Siegmund A, Xi N, Kaplan-Lefko P, Rex K, Chen A, Lin J, Moriguchi J, Berry L, Huang L, Teffera Y, Yang Y, Zhang Y, Bellon SF, Lee M, Shimanovich R, Bak A, Dominguez C, Norman MH, Harmange JC, Dussault I, Kim TS. Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-meth yl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J Med Chem. 2008 Jul 10;51(13):3688-91. Epub 2008 Jun 14. PubMed PMID: 18553959.
