Delving into the Latest Updates on UMB-298 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

p300-CBP transcription factors

Mechanism

p300-CBP transcription factors inhibitors

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

University of Massachusetts Boston

Active Organization

Dana-Farber Cancer Institute, Inc.

University of Massachusetts Boston

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Structure

Molecular FormulaC27H31ClN4O2

InChIKeyNZXSWCLCRDCHGN-UHFFFAOYSA-N

CAS Registry2266569-73-5

The use of epigenetic bromodomain inhibitors as anticancer therapeutics has transitioned from targeting bromodomain extraterminal domain (BET) proteins into targeting non-BET bromodomains. The two most relevant non-BET bromodomain oncology targets are cyclic AMP response element-binding protein (CBP) and E1A binding protein P300 (EP300). To explore the growing CBP/EP300 interest, we developed a highly efficient two-step synthetic route for dimethylisoxazole-attached imidazo[1,2-a]pyridine scaffold-containing inhibitors. Our efficient two-step reactions enabled high-throughput synthesis of compounds designed by molecular modeling, which together with structure-activity relationship (SAR) studies facilitated an overarching understanding of selective targeting of CBP/EP300 over non-BET bromodomains. This led to the identification of a new potent and selective CBP/EP300 bromodomain inhibitor, UMB298 (compound 23, CBP IC₅₀ 72 nM and bromodomain 4, BRD4 IC₅₀ 5193 nM). The SAR we established is in good agreement with literature-reported CBP inhibitors, such as CBP30, and demonstrates the advantage of utilizing our two-step approach for inhibitor development of other bromodomains.

100 Deals associated with UMB-298

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