Delving into the Latest Updates on T-62 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

T 62

Target

Adenosine receptor

Action

agonists

Mechanism

Adenosine receptor agonists

Therapeutic Areas

Infectious DiseasesNervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Chronic PainHerpes ZosterNeuralgia, Postherpetic

Originator Organization

King Pharmaceuticals LLC

Active Organization-

Inactive Organization

Pfizer Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC15H14ClNOS

InChIKeyOTZVBZFYMFTYKH-UHFFFAOYSA-N

CAS Registry40312-34-3

Over the past several decades, invasive fungal infections, especially candidiasis, have caused dramatic morbidity and mortality due to ineffective antifungal drugs and severe drug resistance. Herein, new BRD4-histone deacetylase (HDAC) inhibitors were designed to restore the susceptibility of Candida albicans (C. albicans) to fluconazole (FLC). Interestingly, several compounds showed excellent selectivity against fungal HDACs. In particular, compound B2 showed excellent synergistic effect with FLC against resistant C. albicans (FICI = 0.063) with high selectivity against fungal HDACs (SI = 1653) and low cytotoxicity. Compound B2 effectively synergized with FLC and prevented biofilm formation and morphological transition in resistant C. albicans, potentiating the antifungal activity of FLC in vivo and significantly reducing kidney fungal loads. Thus, this drug combination is promising in the treatment of resistant C. albicans infections.

01 Jan 2021·HETEROCYCLES

Microwave-Assisted Synthesis of 2-Aminothiophene Derivatives via Improved Gewald Reactions

Author: Zhang, Zhiyan ; Huang, Lei ; Ruan, Bankang ; Li, Luolan ; Xu, Chao

In this paper, a new and efficient method was developed to prepare 2-aminothiophene derivatives through improved Gewald reaction.Thirty-one final products were synthesized under microwave radiation for 30 min with 57%-95% isolated yields.All the products could be used as building blocks in drug discovery.

01 Aug 2020·Biochimica et biophysica acta. General subjectsQ3 · BIOLOGY

Retrospective ensemble docking of allosteric modulators in an adenosine G-protein-coupled receptor

Q3 · BIOLOGY

Article

Author: Wang, Jinan ; Bhattarai, Apurba ; Miao, Yinglong

BACKGROUND:

Ensemble docking has proven useful in drug discovery and development. It increases the hit rate by incorporating receptor flexibility into molecular docking as demonstrated on important drug targets including G-protein-coupled receptors (GPCRs). Adenosine A₁ receptor (A₁AR) is a key GPCR that has been targeted for treating cardiac ischemia-reperfusion injuries, neuropathic pain and renal diseases. Development of allosteric modulators, compounds binding to distinct and less conserved GPCR target sites compared with agonists and antagonists, has attracted increasing interest for designing selective drugs of the A₁AR. Despite significant advances, more effective approaches are needed to discover potent and selective allosteric modulators of the A₁AR.

METHODS:

Ensemble docking that integrates Gaussian accelerated molecular dynamic (GaMD) simulations and molecular docking using Autodock has been implemented for retrospective docking of known positive allosteric modulators (PAMs) in the A₁AR.

RESULTS:

Ensemble docking outperforms docking of the receptor cryo-EM structure. The calculated docking enrichment factors (EFs) and the area under the receiver operating characteristic curves (AUC) are significantly increased.

CONCLUSIONS:

Receptor ensembles generated from GaMD simulations are able to increase the success rate of discovering PAMs of A₁AR. It is important to account for receptor flexibility through GaMD simulations and flexible docking.

GENERAL SIGNIFICANCE:

Ensemble docking is a promising approach for drug discovery targeting flexible receptors.

100 Deals associated with T-62

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12919

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic Pain	Phase 2	United States	Pfizer Inc.	25 Jul 2007
Herpes Zoster	Phase 2	United States	Pfizer Inc.	25 Jul 2007
Neuralgia, Postherpetic	Phase 2	United States	Pfizer Inc.	25 Jul 2007