AMG-837

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22217876
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Free fatty acid receptor 1 10 Target ID: CHEMBL4422 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22217876 \| https://www.ncbi.nlm.nih.gov/pubmed/24900872 \| https://www.ncbi.nlm.nih.gov/pubmed/26620255	Partial Agonist 290		41.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24234912 https://www.ncbi.nlm.nih.gov/pubmed/22087278	Primary		Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680520	no

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY115003	https://www.001chemical.com/chem/search?q=DY115003
1PlusChem LLC	1P003D23	https://www.1pchem.com/search?query=1P003D23
AK Scientific	3568AC	https://aksci.com/item_detail.php?cat=3568AC
AbovChem LLC	HY-13967A	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-13967A
AstaTech	P13904	http://astatechinc.com/CPSResult.php?CRNO=P13904
Axon MedChem	2405	https://www.axonmedchem.com/product/2405
BLD Pharm	BD228266	http://www.bldpharm.com/search/Search.html?keyword=BD228266
BLD Pharm	BD630066	http://www.bldpharm.com/search/Search.html?keyword=BD630066
BLD Pharm	BD630928	http://www.bldpharm.com/search/Search.html?keyword=BD630928
BOC Sciences	865231-46-5	http://www.bocsci.com/description.asp?cas=865231-46-5
Chem Scene	CS-3280	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3280
ChemShuttle	157205	https://www.chemshuttle.com/catalogsearch/result/?q=157205
Debye Scientific	DA-35329	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-35329
Enamine	EN300-313172	https://www.enaminestore.com/catalog/EN300-313172
Excenen	EX-A1792	http://www.excenen.com/searchresultlist.php?id=EX-A1792
KeyOrganics	AS-51920	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-51920
Matrix Scientific	97994	http://www.matrixscientific.com/097994.html
MedChem Express	HY-13967B	https://www.medchemexpress.com/search.html?q=HY-13967B&ft=&fa=&fp=
MolPort	MolPort-027-835-210	https://www.molport.com/shop/molecule-link/MolPort-027-835-210
MolPort	MolPort-046-162-883	https://www.molport.com/shop/molecule-link/MolPort-046-162-883
MolPort	MolPort-046-416-984	https://www.molport.com/shop/molecule-link/MolPort-046-416-984
Molcore	MC115003	http://www.molcore.com/CatMC115003.html
MuseChem	I002120	https://www.musechem.com/product/I002120.html
ShangHai Biochempartner	BCP001579	http://www.biochempartner.com/search_BCP001579
Toronto Research Chemicals	A614410	https://www.trc-canada.com/product-detail/?CatNum=A614410
eMolecules	252334936	https://orderbb.emolecules.com/search/#?query=252334936
eMolecules	271447108	https://orderbb.emolecules.com/search/#?query=271447108
eMolecules	275091649	https://orderbb.emolecules.com/search/#?query=275091649
eMolecules	44689103	https://orderbb.emolecules.com/search/#?query=44689103
eMolecules	50282168	https://orderbb.emolecules.com/search/#?query=50282168
eNovation Chemicals	D501843	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501843&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4363387517	https://mcule.com/MCULE-4363387517/
mcule	MCULE-8305184083	https://mcule.com/MCULE-8305184083/
mcule	MCULE-9563676159	https://mcule.com/MCULE-9563676159/

PubMed

Title	Date	PubMed
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	21854074
Identification and pharmacological characterization of multiple allosteric binding sites on the free fatty acid 1 receptor.	2012 Nov	22859723

Patents

Sample Use Guides

In Vivo Use Guide

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 Vitro Use Guide

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


					T5KP187PIU

AMG-837 SODIUM

SALT/SOLVATE -> PARENT

Related Record Type Details


					NE6U6R66U4

AMG-837

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22217876Curator'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

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Overview

OverviewOther

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22217876
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