AMG 337

Catalog No.S8167 Batch:S816701

Technical Data

Formula	C₂₃H₂₂FN₇O₃
Molecular Weight	463.46	CAS No.	1173699-31-4
Solubility (25°C)*	In vitro	DMSO	95 mg/mL (204.97 mM)
		Ethanol	95 mg/mL (204.97 mM)
		Water	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 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the Met (c-Met) receptor with an IC50 of 1 nM.

Targets

MET receptor ^[1] (Cell-free assay)	MET(H1094R) ^[1] (Cell-free assay)	MET(M1250T) ^[1] (Cell-free assay)	MET(V1092I) ^[1] (Cell-free assay)
1 nM	1 nM	4.7 nM	21.5 nM

In vitro

AMG 337 potently inhibits the enzymatic activity of WT MET and a subset of MET mutants found in papillary renal cell carcinoma. The inability of AMG 337 to inhibit the Y1230 and D1228 mutants is likely the result of a disruption of the inactive confirmation of the activation loop in the MET kinase domain. AMG 337 also inhibits cell based HGF-induced MET phosphorylation in PC3 cells with IC50 of 5nM. AMG 337 inhibits proliferation in MET-dependent cancer cell lines. AMG 337 inhibits signaling through the PI3K and MAPK pathways in MET-amplified gastric cancer cell lines resulting in profound effects on cell proliferation and survival^[1].

In vivo

AMG 337 exhibits impressive potency with >90% inhibition of Gab-1 phosphorylation at a dose of 0.75 mg/kg (32 nmol/L free-drug concentration). AMG 337 is well tolerated at continuously administered doses that corresponded with complete MET inhibition for 24 hours, suggesting that AMG 337 has the preclinical attributes required to test the role of MET in human cancer^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Human cancer cell lines Concentrations serial dilution(a top concentration of 3 mmol/L.) Incubation Time 72 h Method To evaluate the effect of AMG 337 on viability, cells are seeded in 96-well plates at an optimal density to ensure proliferation throughout the duration of the experiments. Cells are treated for 72 hours with a 10-point, 3-fold, serial dilution of AMG 337 using a top concentration of 3 mmol/L. Viability is measured with the CellTiter-Glo Luminescent Cell Viability Assay.
Animal Study:^{^[1]}	Animal Models Female CD1 nu/nu or athymic nude mice(Tumor xenograft models) Dosages 0.1, 0.5, 0.75, 1, 2, or 3 mg/kg Administration by oral gavage

Cell Assay:^{^[1]}

Cell lines
Human cancer cell lines
Concentrations
serial dilution(a top concentration of 3 mmol/L.)
Incubation Time
72 h
Method
To evaluate the effect of AMG 337 on viability, cells are seeded in 96-well plates at an optimal density to ensure proliferation throughout the duration of the experiments. Cells are treated for 72 hours with a 10-point, 3-fold, serial dilution of AMG 337 using a top concentration of 3 mmol/L. Viability is measured with the CellTiter-Glo Luminescent Cell Viability Assay.

Animal Study:^{^[1]}

Animal Models
Female CD1 nu/nu or athymic nude mice(Tumor xenograft models)
Dosages
0.1, 0.5, 0.75, 1, 2, or 3 mg/kg
Administration
by oral gavage

References

[1] Hughes PE, et al. Mol Cancer Ther. 2016, 15(7):1568-1579.

Selleck's AMG 337 has been cited by 2 publications

SRC kinase activator CDCP1 promotes hepatocyte growth factor-induced cell migration/invasion of a subset of breast cancer cells [ J Biol Chem, 2022, S0021-9258(22)00070-9]	PubMed: 35085554
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer. [ Cancer Cell, 2019, 36(1):35-50]	PubMed: 31287991

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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.