PF-05089771

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H12Cl2FN5O3S2
Molecular Weight	500.354
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C(C=NN1)C2=CC(Cl)=CC=C2OC3=CC(F)=C(C=C3Cl)S(=O)(=O)NC4=CSC=N4

InChI

InChIKey=ZYSCOUXLBXGGIM-UHFFFAOYSA-N

InChI=1S/C18H12Cl2FN5O3S2/c19-9-1-2-14(10(3-9)11-6-24-25-18(11)22)29-15-5-13(21)16(4-12(15)20)31(27,28)26-17-7-30-8-23-17/h1-8,26H,(H3,22,24,25)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29578944 | https://www.ncbi.nlm.nih.gov/pubmed/26419464 | https://www.ncbi.nlm.nih.gov/pubmed/25060923 | https://www.ncbi.nlm.nih.gov/pubmed/26895021 | https://adisinsight.springer.com/drugs/800026875

PF-05089771 is an oral administrated Nav1.7 channel inhibitor. PF-05089771 provided the best opportunity to explore Nav1.7 blockade for the treatment of acute or chronic pain conditions. PF-05089771 has completed Phase II clinical trials of third molar extraction and primary inherited erythromelalgia. The magnitude of efficacy of PF-05089771 in the randomized, placebo-controlled, double-blind clinical study in subjects with painful diabetic peripheral neuropathy was disappointing. Although there was a trend towards a reduction in pain and improvement in sleep rating in patients with painful DPN when compared to placebo treatment, this was not statistically significant.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium channel protein type IX alpha subunit 21 Target ID: CHEMBL4296 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27050761	Blocker 537	0.011 µM [IC50]
Sodium channel protein type VIII alpha subunit 7 Target ID: CHEMBL5202 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27050761	Blocker 537	0.16 µM [IC50]
Sodium channel protein type V alpha subunit 49 Target ID: CHEMBL1980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27050761	Blocker 537	25.0 µM [IC50]
Sodium channel protein type I alpha subunit 15 Target ID: CHEMBL1845 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27050761	Blocker 537	0.85 µM [IC50]
Sodium channel protein type II alpha subunit 27 Target ID: CHEMBL4187 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27050761	Blocker 537	0.11 µM [IC50]

PubMed

Title	Date	PubMed
Recent progress in sodium channel modulators for pain.	2014 Aug 15	25060923
Primary erythromelalgia: a review.	2015 Sep 30	26419464
Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release.	2016	27050761
Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia.	2016 Apr 20	27099175
Clinical Micro-Dose Studies to Explore the Human Pharmacokinetics of Four Selective Inhibitors of Human Nav1.7 Voltage-Dependent Sodium Channels.	2016 Jul	26895021
The Selective Nav1.7 Inhibitor, PF-05089771, Interacts Equivalently with Fast and Slow Inactivated Nav1.7 Channels.	2016 Nov	27587537
Discovery of Clinical Candidate 4-[2-(5-Amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide (PF-05089771): Design and Optimization of Diaryl Ether Aryl Sulfonamides as Selective Inhibitors of Na(V)1.7.	2017 Aug 24	28682065
Efficacy of the Nav1.7 blocker PF-05089771 in a randomised, placebo-controlled, double-blind clinical study in subjects with painful diabetic peripheral neuropathy.	2018 Aug	29578944
Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors.	2018 Jan 23	29311306

Sample Use Guides

In Vivo Use Guide

Single doses of 150 mg, 450 mg and 1600 mg

Route of Administration: Oral

Name

Type

Language

PF-05089771

Common Name

English

BENZENESULFONAMIDE, 4-(2-(3-AMINO-1H-PYRAZOL-4-YL)-4-CHLOROPHENOXY)-5-CHLORO-2-FLUORO-N-4-THIAZOLYL-

Systematic Name

English

Code System Code Type Description

PUBCHEM

46840946