ChemicalBook > CAS DataBase List > AMG 458

AMG 458

Product Name
AMG 458
CAS No.
913376-83-7
Chemical Name
AMG 458
Synonyms
CS-530;AMG 458;AMG458/AMG-458;AMG-458 ，S2747;AMG 458 USP/EP/BP;AMG-458（913376-83-7）;AMG-458, 10 mM in DMSO;AMG-458 AMG458 c-MET inhibitor;AMG458,inhibit,Inhibitor,c-Met/HGFR,AMG-458;1-(2-Hydroxy-2-methylpropyl)-N-[5-[(7-methoxyquinolin-4-yl)oxy]pyridin-2-yl]-5-methyl-3-oxo-2-
CBNumber
CB62500951
Molecular Formula
C30H29N5O5
Formula Weight
539.58
MOL File
913376-83-7.mol
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AMG 458 Property

Density 
1.339
storage temp. 
Store at -20°C
solubility 
Soluble in DMSO
form 
Powder
color 
Off-white to pink
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Hazard and Precautionary Statements (GHS)

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N-Bromosuccinimide Price

TRC
Product number
A614415
Product name
AMG-458
Packaging
10mg
Price
$415
Updated
2021/12/16
Biosynth Carbosynth
Product number
FA64937
Product name
AMG 458
Packaging
1mg
Price
$120
Updated
2021/12/16
Adipogen Life Sciences
Product number
SYN-1144-M001
Product name
AMG-458
Purity
≥95%
Packaging
1mg
Price
$135
Updated
2021/12/16
Biosynth Carbosynth
Product number
FA64937
Product name
AMG 458
Packaging
2mg
Price
$180
Updated
2021/12/16
Biosynth Carbosynth
Product number
FA64937
Product name
AMG 458
Packaging
5mg
Price
$250
Updated
2021/12/16
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AMG 458 Chemical Properties,Usage,Production

Uses

AMG-458 is a potent inhibitor of c-Met with an IC50 of 60 nM.

Biological Activity

amg-458 is a potent and selective inhibitor of human and mouse c-met with ic50 value of 1.2 nm and 2.0 nm respectively.c-met, also known as hepatocyte growth factor receptor, is a receptor tyrosine kinase that can be activated by hepatocyte growth factor/scatter factor (hgf/sf). it is a membrane protein which plays an essential role in embryonic development and wound healing.recent study investigated the effect of amg-456 treatment on cell radiosensitizing response. the results showed that amg-458 treatment enhanced radiosensitivity in h441 with higher levels of c-met but not in a549 with lower expression of c-met [1].this component was also used in an animal model to study the role of c-met in the development of tumor. for instance, orally administration of amg-456 resulted in significant inhibition of tumor growth in /tpr-met and u-87 mg xenograft models without any adverse effect on body weight [2].

in vivo

AMG-458 (orally, 30, 100 mg/kg) significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight[1].

Animal Model:NIH-3T3/TPR-Met model and U-87 MG human glioblastoma xenograft model[1].
Dosage:10, 30, 100 mg/kg.
Administration:Orally q.d. or b.i.d.
Result:With an ED50 of ～12 mg/kg and an ED90 of ～ 34 mg/kg in NIH-3T3/TPR-Met model.
With an ED50 of ～16 mg/kg and an ED90 of ～ 59 mg/kg in U-87 MG human glioblastoma xenograft model.
Significantly inhibited tumor growth at 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d. without adverse effect on body weight.
Animal Model:Balb/c mouse and SD rat[1].
Dosage:1 mg/kg (Pharmacokinetic Analysis).
Administration:IV dose: 1 mg/kg (20% Captisol with pH adjusted to 3.5 using methanesulfonic acid).
Result:Exhibited CL ((L/h)/kg) values of 0.16 and 0.73, Vss (L/kg) values of 0.31 and 0.62, t1/2 (h) values of 1.3 and 1.0 in mouse and rat, respectively.

Enzyme inhibitor

This potent c-Met protein kinase inhibitor (FW = 539.58 g/mol; CAS 913376-83-7; Solubility: 21 mg/mL DMSO; ~1 mg/mL H2O), also named 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin- 2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide, targets the MET proto-oncogene product c-Met, which is the hepatocyte growth factor receptor possessing tyrosine-kinase activity. The primary single-chain precursor protein is posttranslationally cleaved to produce the a and b subunits that are disulfide linked to form the mature receptor. Various mutations in the MET gene are associated with papillary renal carcinoma. AMG-458 preferentially inhibits c-Met (Ki = 1.2 nM), showing ~350-fold greater potency than VEGFR2 in cells. AMG-458 significantly inhibited tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight. AMG 458 binds covalently to liver microsomal proteins from rats and humans, even in the absence of NADPH. When [14C]AMG-458 is incubated with liver microsomes in the presence of glutathione or N-acetyl cysteine, quinolone-type thioether adducts can be detected by radiochromatographyand LC/MS/MS analysis. AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c- Met and p-Met in non-small cell lung cancer (NSCLC) tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

target

c-Met (H1094R)

IC 50

VEGDR2: 4100 nM (Ki)

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 2012,84:e525-531.2. liu l, siegmund a, xi n, kaplan-lefko p, rex k, chen a, et al. 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 2008,51:3688-3691.

AMG 458 Preparation Products And Raw materials

Raw materials

Preparation Products

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AMG 458 Suppliers

China 69 United Kingdom 2 United States 17 Global 88
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913376-83-7, AMG 458Related Search:

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  • AMG 458
  • 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
  • 1-(2-Hydroxy-2-methylpropyl)-N-[5-[(7-methoxyquinolin-4-yl)oxy]pyridin-2-yl]-5-methyl-3-oxo-2-
  • CS-530
  • 1H-Pyrazole-4-carboxamide, 2,3-dihydro-1-(2-hydroxy-2-methylpropyl)-N-[5-[(7-methoxy-4-quinolinyl)oxy]-2-pyridinyl]-5-methyl-3-oxo-2-phenyl-
  • AMG 458 USP/EP/BP
  • AMG-458 AMG458 c-MET inhibitor
  • AMG458,inhibit,Inhibitor,c-Met/HGFR,AMG-458
  • AMG458/AMG-458
  • AMG-458, 10 mM in DMSO
  • AMG-458（913376-83-7）
  • AMG-458 ，S2747
  • 913376-83-7
  • Inhibitors