Name: AMG-458
Brand: Selleck Chemicals
SKU: S2747
Availability: InStock
Rating: 5 (1 reviews)

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Quality Control

Batch: Purity: 99.89%

99.89

Related Targets	EGFR VEGFR PDGFR FGFR Src MEK CSF-1R FLT3 HER2 c-Kit
Other c-Met Inhibitors	Tepotinib Dihexa SGX-523 PHA-665752 Foretinib SU11274 BMS-777607 JNJ-38877605 Tivantinib PF-04217903

Solubility

In vitro
Batch:

DMSO : 26 mg/mL (48.18 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	15% Captisol 1 citrate vehicle Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (18.53mM)	Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 15% Captisol+citrate vehicle clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	539.58	Formula	C₃₀H₂₉N₅O₅	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	913376-83-7	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			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

Mechanism of Action

Features	Completely bioavailable across species and the intrinsic half-life is increased in higher mammals.
Targets/IC₅₀/Ki	c-Met (H1094R) 0.5 nM(Ki) c-Met (V1092I) 1.1 nM(Ki) c-Met (Human) 1.2 nM(Ki) c-Met (Mouse) 2.0 nM(Ki) c-Met (D1228H) 2.2 nM(Ki) c-Met (M1250T) 4.1 nM(Ki) c-Met (Y1230H) 4.5 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. 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. 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.
In vivo	AMG 458 is metabolically stable in the liver microsomes of mouse, rat, dog, monkey, and human with low intrinsic clearances (Cl_int: <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. High concentrations of AMG 458 in some organs may produce toxicity via oxidative stress.
References	[1] https://pubmed.ncbi.nlm.nih.gov/18553959/ [2] https://pubmed.ncbi.nlm.nih.gov/18837519/ [3] https://pubmed.ncbi.nlm.nih.gov/22836051/

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AMG-458 c-Met inhibitor

Chemical Structure

Molecular Weight: 539.58