Delving into the Latest Updates on SMD-3040 with Synapse

Overview

Basic Info

Drug Type

Proteolysis-targeting chimeras (PROTAC)

Synonyms

Target

SMARCA2

Mechanism

SMARCA2 degraders(Probable global transcription activator SNF2L2 degraders)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

University of Michigan

Active Organization

University of Michigan

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC52H66N10O5S

InChIKeyGMCWCUOAGNWNLO-YTZIVEPUSA-N

CAS Registry-

SMARCA2 is an attractive synthetic lethality target for human cancers with SMARCA4 deficiency. Herein, we report the design, synthesis, and biological evaluation of selective SMARCA2 protein degraders developed using the proteolysis targeting chimera (PROTAC) technology. Our efforts have led to the discovery of a series of potent and selective SMARCA2 degraders, exemplified by SMD-3040. SMD-3040 degrades SMARCA2 protein with a low nanomolar DC₅₀ and D_max > 90% and demonstrates an excellent degradation selectivity for SMARCA2 protein over SMARCA4 protein. It displays potent cell growth inhibitory activity in a panel of SMARCA4-deficient cancer cell lines and has much weaker activity in SMARCA4 wild-type cancer cell lines. SMD-3040 achieves strong tumor growth inhibition in two SMARCA4-deficient xenograft models at well-tolerated dose schedules. Further optimization of SMD-3040 may lead to the discovery of new therapies for the treatment of human cancers with SMARCA4 deficiency.

100 Deals associated with SMD-3040

Login to view more data