af-353 has been researched along with Pain* in 3 studies
3 other study(ies) available for af-353 and Pain
| Article | Year |
|---|---|
Identification of selective mtbDHFR inhibitors by virtual screening and experimental approaches.
mtbDHFR-targeting inhibition has become a promising approach for tuberculosis treatment. In the current research, a multi-step virtual screening effort toward ZINC and MCE databases was devoted to discover novel mtbDHFR inhibitors. Based on binding affinity of small molecules through molecular docking study in AutoDock Vina, the number of compounds was reduced to 952,688. Further, these compounds were employed by a step-by-step multiple docking programs of Schrödinger suite and filtered by pharmacokinetics and PAINS parameters. Finally, nine ZINC compounds and 400 MCE compounds were obtained. These compounds of binding ability were tested with mtbDHFR by FluoPol-ABPP approach established in this work. Finally, AF-353 compound was found to have strong binding effect to mtbDHFR. AF-353 was further tested for mtb and hDHFR enzymatic activities, and it was proved to possess 50-fold selectivity toward mtbDHFR over hDHFR. In silico MD simulation results supported this selectivity. Topics: Computer Simulation; Databases, Factual; Humans; Molecular Docking Simulation; Pain | 2022 |
Identification and SAR of novel diaminopyrimidines. Part 2: The discovery of RO-51, a potent and selective, dual P2X(3)/P2X(2/3) antagonist for the treatment of pain.
The purinoceptor subtypes P2X(3) and P2X(2/3) have been shown to play a pivotal role in models of various pain conditions. Identification of a potent and selective dual P2X(3)/P2X(2/3) diaminopyrimidine antagonist RO-4 prompted subsequent optimization of the template. This paper describes the SAR and optimization of the diaminopyrimidine ring and particularly the substitution of the 2-amino group. The discovery of the highly potent and drug-like dual P2X(3)/P2X(2/3) antagonist RO-51 is presented. Topics: Adenosine Triphosphate; Analgesics; Animals; Chemistry, Pharmaceutical; CHO Cells; Cricetinae; Cricetulus; Drug Design; Drug Evaluation, Preclinical; Humans; Inhibitory Concentration 50; Models, Chemical; Pain; Purinergic P2 Receptor Antagonists; Pyrimidines; Receptors, Purinergic P2; Structure-Activity Relationship | 2009 |
Identification and SAR of novel diaminopyrimidines. Part 1: The discovery of RO-4, a dual P2X(3)/P2X(2/3) antagonist for the treatment of pain.
P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X(3) and P2X(2/3) receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X(3)/P2X(2/3) antagonists offer significant potential for the treatment of pain. A high-throughput screen of the Roche compound collection resulted in the identification of a novel series of diaminopyrimidines; subsequent optimization resulted in the discovery of RO-4, a potent, selective and drug-like dual P2X(3)/P2X(2/3) antagonist. Topics: Adenosine Triphosphate; Analgesics; Chemistry, Pharmaceutical; Drug Design; Drug Evaluation, Preclinical; Humans; Inhibitory Concentration 50; Ions; Ligands; Models, Chemical; Pain; Purinergic P2 Receptor Antagonists; Pyrimidines; Receptors, Purinergic P2; Structure-Activity Relationship | 2009 |