Delving into the Latest Updates on JNJ-65234637 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

BCL6

Mechanism

BCL6 inhibitors(B-cell lymphoma 6 protein inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Janssen Research & Development LLC

Active Organization

Janssen Research & Development LLC

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC29H28ClF3N8O4

InChIKeyLGAFZGSECXDYIR-ZDUSSCGKSA-N

CAS Registry2360625-97-2

Author: Isaac, Methvin B. ; Phillippar, Ulrike ; Lu, Tianbao ; Packman, Kathryn ; Mamai, Ahmed ; Chau, Anh M. ; Privé, Gilbert G. ; Morshed, Monzur M. ; Kiyota, Taira ; Undzys, Elijus ; Kuntz, Douglas A. ; Uehling, David E. ; Aman, Ahmed ; Strathdee, Graig ; Connolly, Pete ; Al-awar, Rima ; Subramanian, Pandiaraju R. ; Abibi, Ayome ; Attar, Riccardo ; Chan, Manuel ; Poda, Gennady ; Edwards, James ; O’Meara, Jeff ; Austin, Nigel ; Winston, Jeffrey ; Du Jardin, Marc ; Prakesch, Michael A. ; Subramaniam, Ratheesh ; Mohammed, Mohammed ; Nguyen, Kong ; Marcellus, Richard ; Morin, Justin A. ; Wilson, Brian J. ; Pomroy, Neil C. ; Theriault, Brigitte ; Joseph, Babu B. ; Watson, Iain D.

B cell lymphoma 6 (BCL6), a highly regulated transcriptional repressor, is deregulated in several forms of non-Hodgkin lymphoma (NHL), most notably in diffuse large B-cell lymphoma (DLBCL). The activities of BCL6 are dependent on protein-protein interactions with transcriptional co-repressors. To find new therapeutic interventions addressing the needs of patients with DLBCL, we initiated a program to identify BCL6 inhibitors that interfere with co-repressor binding. A virtual screen hit with binding activity in the high micromolar range was optimized by structure-guided methods, resulting in a novel and highly potent inhibitor series. Further optimization resulted in the lead candidate 58 (OICR12694/JNJ-65234637), a BCL6 inhibitor with low nanomolar DLBCL cell growth inhibition and an excellent oral pharmacokinetic profile. Based on its overall favorable preclinical profile, OICR12694 is a highly potent, orally bioavailable candidate for testing BCL6 inhibition in DLBCL and other neoplasms, particularly in combination with other therapies.

100 Deals associated with JNJ-65234637

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