PF-04991532

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H19F3N4O3
Molecular Weight	396.3637
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)C1=CC=C(NC(=O)[C@H](CC2CCCC2)N3C=NC(=C3)C(F)(F)F)N=C1

InChI

InChIKey=GKMLFBRLRVQVJO-ZDUSSCGKSA-N

InChI=1S/C18H19F3N4O3/c19-18(20,21)14-9-25(10-23-14)13(7-11-3-1-2-4-11)16(26)24-15-6-5-12(8-22-15)17(27)28/h5-6,8-11,13H,1-4,7H2,(H,27,28)(H,22,24,26)/t13-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C18H19F3N4O3
Molecular Weight	396.3637
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/22196621 | https://www.ncbi.nlm.nih.gov/pubmed/25384899
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800032199

Pfizer was developing PF-04991532, a potent and selective hepatoselective glucokinase activator. PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. F-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. PF-04991532 may offer glycemic control without inducing hepatic steatosis supporting the evaluation of tissue specific activators in clinical trials. In 2012, Pfizer discontinued the development of the compound.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hexokinase type IV 6 Target ID: CHEMBL3820 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22196621	Activator 1430		90.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: https://clinicaltrials.gov/ct2/show/NCT01336738 http://adisinsight.springer.com/drugs/800032199	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1436 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30747552	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04991532 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3669 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30747552	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04991532 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1898 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30747552	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04991532 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
MolPort	MolPort-046-162-916	https://www.molport.com/shop/molecule-link/MolPort-046-162-916
Molnova	M10804	https://www.molnova.com/en/serch-list.html?keywords=M10804
MuseChem	M141433	https://www.musechem.com/product/M141433.html
eMolecules	50427965	https://orderbb.emolecules.com/search/#?query=50427965

PubMed

Title	Date	PubMed
The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats.	2014	24858947
Comparison of the circulating metabolite profile of PF-04991532, a hepatoselective glucokinase activator, across preclinical species and humans: potential implications in metabolites in safety testing assessment.	2015 Feb	25384899

Patents

Sample Use Guides

In Vivo Use Guide

Tablets 150 mg - 750 mg, all once daily for 84 days

Route of Administration: Oral

In Vitro Use Guide

PF-04991532 activated human recombinant glucokinase with EC50 90nM

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:55:53 GMT 2023` Edited by `admin` on `Sat Dec 16 01:55:53 GMT 2023`
Record UNII	AJ212MS2O2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PF-04991532

Common Name

English

3-PYRIDINECARBOXYLIC ACID, 6-(((2S)-3-CYCLOPENTYL-1-OXO-2-(4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL)PROPYL)AMINO)-

Systematic Name

English

Code System Code Type Description

CAS

1215197-37-7