PF-06282999

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H12ClN3O3S
Molecular Weight	325.771
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(Cl)C=C1C2=CC(=O)NC(=S)N2CC(N)=O

InChI

InChIKey=ICYNYWFGIDGBRD-UHFFFAOYSA-N

InChI=1S/C13H12ClN3O3S/c1-20-10-3-2-7(14)4-8(10)9-5-12(19)16-13(21)17(9)6-11(15)18/h2-5H,6H2,1H3,(H2,15,18)(H,16,19,21)

HIDE SMILES / InChI

Molecular Formula	C13H12ClN3O3S
Molecular Weight	325.771
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30889221 | https://adisinsight.springer.com/drugs/800036418 | https://www.ncbi.nlm.nih.gov/pubmed/28685622

PF-06282999 is selective myeloperoxidase inactivator. PF-06282999 selectively activated human pregnane X receptor (PXR). Treatment of human HepaRG cells with PF-06282999 led to ∼14-fold induction in CYP3A4 mRNA and 5-fold increase in midazolam-1'-hydroxylase activity. [18F]-Fluoro-deoxy-glucose (FDG) was administered to Ldlr-/- mice with established atherosclerosis that had been treated with clinically relevant doses of PF-06282999, and reduced FDG signal was observed in animals treated with a dose of PF-06282999 that corresponded with reduced necrotic core area. PF-06282999 was developed for the treatment of acute coronary syndromes.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Myeloperoxidase 6 Target ID: CHEMBL2439 Sources: https://adisinsight.springer.com/drugs/800036418	Inhibitor 8297		1.9 µM [IC50]

PubMed

Title	Date	PubMed
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.	2015 Nov 12	26509551
Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans.	2016 Feb	26608081
Examination of the Human Cytochrome P4503A4 Induction Potential of PF-06282999, an Irreversible Myeloperoxidase Inactivator: Integration of Preclinical, In Silico, and Biomarker Methodologies in the Prediction of the Clinical Outcome.	2017 May	28254951
Induction of human cytochrome P450 3A4 by the irreversible myeloperoxidase inactivator PF-06282999 is mediated by the pregnane X receptor.	2018 Jul	28685622
Establishing Transcriptional Signatures to Differentiate PXR-, CAR-, and AhR-Mediated Regulation of Drug Metabolism and Transport Genes in Cryopreserved Human Hepatocytes.	2018 May	29440451
Myeloperoxidase inhibition in mice alters atherosclerotic lesion composition.	2019	30889221

Sample Use Guides

In Vivo Use Guide

5 and 15 mg/kg twice a day

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:52:01 UTC 2023` Edited by `admin` on `Sat Dec 16 11:52:01 UTC 2023`
Record UNII	YO3O4Q2NC8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PF-06282999

Common Name

English

1(2H)-PYRIMIDINEACETAMIDE, 6-(5-CHLORO-2-METHOXYPHENYL)-3,4-DIHYDRO-4-OXO-2-THIOXO-

Systematic Name

English

2-(6-(5-CHLORO-2-METHOXYPHENYL)-4-OXO-2-THIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)ACETAMIDE

Systematic Name

English

Code System Code Type Description

PUBCHEM

71571306