AMG-458

Catalog No.S2747 Batch:S274701

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Technical Data

Formula

C30H29N5O5
Molecular Weight 539.58 CAS No. 913376-83-7
Solubility (25°C)* In vitro DMSO 21 mg/mL (38.91 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description AMG 458 is a potent c-Met inhibitor with Ki of 1.2 nM, ~350-fold selectivity for c-Met than VEGFR2 in cells.
Targets
c-Met (H1094R) [1] c-Met (V1092I) [1] c-Met (Human) [1] c-Met (Mouse) [1] c-Met (D1228H) [1] View More
0.5 nM(Ki) 1.1 nM(Ki) 1.2 nM(Ki) 2.0 nM(Ki) 2.2 nM(Ki)
In vitro AMG 458 also inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM. [1] AMG 458 is observed to bind covalently to liver microsomal proteins from rats and humans in the absence of NADPH. AMG 458 is believed to react with thiol groups in proteins, producing a methoxy quinoline thioether conjugate. [2] A recent study shows that the constitutive phosphorylation of c-Met in H441 is abrogated by AMG 458. The basal and HGF-induced phosphorylation of c-Met in A549 is attenuated by AMG 458. The combination of radiation therapy and AMG 458 treatment is found to synergistically increase apoptosis in the H441 cell line by reduction of p-Akt and p-Erk levels, but not in A549. [3]
In vivo AMG 458 is metabolically stable in the liver microsomes of mouse, rat, dog, monkey, and human with low intrinsic clearances (Clint: <5, 62, 8, 8, 18 (μL/min)/mg, respectively). When administered orally, AMG 458 achieves remarkably high bioavailability in all species tested. Oral dosing of AMG 458 inhibits HGF-mediated c-Met phosphorylation with an approximate ED90 of 30 mg/kg and an associated plasma exposure of approximately 15 μM at 6 hours. AMG 458 significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models at 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d.with no adverse effect on body weight. [1] High concentrations of AMG 458 in some organs may produce toxicity via oxidative stress. [2]
Features Completely bioavailable across species and the intrinsic half-life is increased in higher mammals.

Protocol (from reference)

Animal Study:

[1]
  • Animal Models

    NIH3T3/TPR-Met and U-87 MG xenograft models are established in female CD-1 nu/nu mice aged 6-8 weeks.

  • Dosages

    10, 30 or 100 mg/kg

  • Administration

    Administered via i.v. or p.o.

RETURN POLICY
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.