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Purity: ≥98%
AMG 458 (AMG-458) is a novel c-Met inhibitor with potential anticancer activity. With a Ki of 1 ~ 2.0 nM, it inhibits c-Met. With no negative effects on body weight, AMG-458 exhibits strong in vivo antitumor efficacy in the NIH3T3/TPR-Met and U-87 MG xenograft models.
| Targets |
c-Met(H1094R) (Ki = 0.5 nM); c-Met(V1092I) (Ki = 1.1 nM); c-Met(Human) (Ki = 1.2 nM); c-Met(Mouse) (Ki = 2.0 nM); c-Met(D1228H) (Ki = 2.2 nM)
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| ln Vitro |
AMG 458 also has an IC50 of 60 and 120 nM, respectively, to inhibit HGF-mediated c-Met phosphorylation in PC3 and CT26 cells.[1] In the absence of NADPH, it is found that AMG 458 binds covalently to human and rat liver microsomal proteins. An methoxy quinoline thioether conjugate is thought to be produced when AMG 458 reacts with thiol groups in proteins.[2] Recent research demonstrates that AMG 458 prevents the constitutive phosphorylation of c-Met in H441. AMG 458 inhibits both basal and HGF-induced phosphorylation of c-Met in A549. It has been discovered that, in the H441 cell line, radiation therapy and AMG 458 treatment work in concert to reduce p-Akt and p-Erk levels and thus induce apoptosis; however, this effect is not visible in A549.[3]
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| ln Vivo |
AMG 458 is metabolically stable with low intrinsic clearances (Clint: <5, 62, 8, 8, 18 (μL/min)/mg) in the liver microsomes of mice, rats, dogs, monkeys, and humans, respectively. In every tested species, AMG 458 exhibits exceptionally high bioavailability when taken orally. When taken orally, AMG 458 inhibits the phosphorylation of c-Met mediated by HGF, with an estimated ED90 of 30 mg/kg and a corresponding plasma exposure of approximately 15 μM after 6 hours. With no negative effects on body weight, AMG 458 significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models at doses of 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d.[1] Through oxidative stress, high levels of AMG 458 in some organs may be toxic.[2]
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| Enzyme Assay |
AMG 458 has a Ki of 1 nM ~ 2.0 nM, making it a strong c-Met inhibitor. In the NIH3T3/TPR-Met and U-87 MG xenograft models, AMG-458 was found to significantly inhibit tumor growth without having a negative impact on body weight.
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| Cell Assay |
AMG 458 also has an IC50 of 60 and 120 nM, respectively, to inhibit HGF-mediated c-Met phosphorylation in PC3 and CT26 cells.
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| Animal Protocol |
NIH-3T3/TPR-Met model and U-87 MG human glioblastoma xenograft model.
10, 30, 100 mg/kg. Orally q.d. or b.i.d. |
| References |
| Molecular Formula |
C30H29N5O5
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| Molecular Weight |
539.58
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| Exact Mass |
539.22
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| Elemental Analysis |
C, 66.78; H, 5.42; N, 12.98; O, 14.83
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| CAS # |
913376-83-7
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CC1=C(C(=O)N(N1CC(C)(C)O)C2=CC=CC=C2)C(=O)NC3=NC=C(C=C3)OC4=C5C=CC(=CC5=NC=C4)OC
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| InChi Key |
GLBZSOQDAOLMGC-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
1-(2-hydroxy-2-methylpropyl)-N-[5-(7-methoxyquinolin-4-yl)oxypyridin-2-yl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide
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| Synonyms |
AMG-458; AMG 458; AMG458
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8533 mL | 9.2665 mL | 18.5329 mL | |
| 5 mM | 0.3707 mL | 1.8533 mL | 3.7066 mL | |
| 10 mM | 0.1853 mL | 0.9266 mL | 1.8533 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
J. Med. Chem. 2008, 51, 3688–3691 |
Chem. Res. Toxicol. 2008, 21, 2216–2222 |
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