Delving into the Latest Updates on BMS-986313 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

RARγ inverse agonists(Retinoic acid receptor gamma inverse agonists), RORγt inverse agonists(RAR-related orphan receptor gamma 2 inverse agonists)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication

Psoriasis

Inactive Indication-

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol-Myers Squibb India Pvt Ltd.

Bristol Myers Squibb Co.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Beaudoin-Bertrand, Myra ; Li, Sha ; Sack, John S. ; Khandelwal, Purnima ; Xiao, Zili ; Denton, Rex ; Basha, Mushkin ; Wang, Jinhong ; Marcoux, David ; Stefanski, Kevin ; Salter-Cid, Luisa ; Babu, Venkatesh ; Obermeier, Mary T. ; Gupta, Arun Kumar ; Shuster, David J. ; Weigelt, Carolyn A. ; Xie, Jenny H. ; Yang, Michael G. ; Mathur, Arvind ; Wu, Dauh-Rurng ; Cornelius, Georgia ; Sherry, Tara ; Karmakar, Ananta ; Fura, Aberra ; Yip, Shiuhang ; Dhar, T. G. Murali ; Zhao, Qihong ; Yarde, Melissa ; Ruzanov, Max

SAR efforts directed at identifying RORγt inverse agonists structurally different from our clinical compound 1 (BMS-986251) led to tricyclic-carbocyclic analogues represented by 3-7 and culminated in the identification of 3d (BMS-986313), with structural differences distinct from 1. The X-ray co-crystal structure of 3d with the ligand binding domain of RORγt revealed several key interactions, which are different from 1. The in vitro and in vivo PK profiles of 3d are described. In addition, we demonstrate robust efficacy of 3d in two preclinical models of psoriasis-the IMQ-induced skin lesion model and the IL-23-induced acanthosis model. The efficacy seen with 3d in these models is comparable to the results observed with 1.

100 Deals associated with BMS-986313

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