AMG-458

    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.


Price and Availability

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AMG-458, purity > 98%, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

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


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


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

  
 
 
 


References

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.