U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C26H21F3O3
Molecular Weight 438.4383
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMG-837

SMILES

CC#C[C@@H](CC(O)=O)C1=CC=C(OCC2=CC(=CC=C2)C3=CC=C(C=C3)C(F)(F)F)C=C1

InChI

InChIKey=ZOPNBMMVVZRSGH-NRFANRHFSA-N
InChI=1S/C26H21F3O3/c1-2-4-21(16-25(30)31)20-9-13-24(14-10-20)32-17-18-5-3-6-22(15-18)19-7-11-23(12-8-19)26(27,28)29/h3,5-15,21H,16-17H2,1H3,(H,30,31)/t21-/m0/s1

HIDE SMILES / InChI

Molecular Formula C26H21F3O3
Molecular Weight 438.4383
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24900872 https://www.ncbi.nlm.nih.gov/pubmed/22087278

AMG-837 is an orally bioavailable partial agonist of the GPR40 (EC50 value 13.5 nM for AMG 837 stimulated Ca2 flux in CHO cells expressing human GPR40) with a superior pharmacokinetic profile. AMG837 stimulated robust glucose-dependent insulin secretion (EC50 value 142±20 nM) in isolated rodent islets, and lowered post-prandial glucose in normal rats. Acute administration of AMG-837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG-837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. AMG-837 exhibits a potential utility for the treatment of type 2 diabetes. Amgen removed AMG-837 from Phase I clinical trials due to concerns over toxicity.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Identification of a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with favorable physicochemical and in vitro ADME properties.
2011 Oct 13
Identification and pharmacological characterization of multiple allosteric binding sites on the free fatty acid 1 receptor.
2012 Nov
Patents

Sample Use Guides

AMG-837 was dosed at 0.03, 0.1 and 0.3 mg/kg by oral gavage daily for 21-days.
Route of Administration: Oral
In CHO cells transiently transfected with human GPR40 and aequorin, AMG-837 stimulated Ca2+ flux with an EC50 of 13.5+/-0.8 nM on the human GPR40 receptor
Substance Class Chemical
Created
by admin
on Sat Dec 16 10:45:49 GMT 2023
Edited
by admin
on Sat Dec 16 10:45:49 GMT 2023
Record UNII
NE6U6R66U4
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMG-837
Common Name English
BENZENEPROPANOIC ACID, .BETA.-1-PROPYN-1-YL-4-((4'-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-3-YL)METHOXY)-, (.BETA.S)-
Systematic Name English
Code System Code Type Description
FDA UNII
NE6U6R66U4
Created by admin on Sat Dec 16 10:45:49 GMT 2023 , Edited by admin on Sat Dec 16 10:45:49 GMT 2023
PRIMARY
PUBCHEM
46854655
Created by admin on Sat Dec 16 10:45:49 GMT 2023 , Edited by admin on Sat Dec 16 10:45:49 GMT 2023
PRIMARY
CAS
865231-46-5
Created by admin on Sat Dec 16 10:45:49 GMT 2023 , Edited by admin on Sat Dec 16 10:45:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID00676764
Created by admin on Sat Dec 16 10:45:49 GMT 2023 , Edited by admin on Sat Dec 16 10:45:49 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY