Delving into the Latest Updates on 35-t with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

ERα x Tubulin

Mechanism

ERα antagonists(Estrogen receptor alpha antagonists), Tubulin inhibitors

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Wuhan University

Active Organization

Wuhan University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC33H31F4N3O5SSe

InChIKeyUBCZFNCFEZWGPP-UHFFFAOYSA-N

CAS Registry2922929-63-1

Endocrine resistance remains a significant problem in the clinical treatment of estrogen receptor α-positive (ERα⁺) breast cancer (BC). In this study, we developed a series of novel dual-functional ERα degraders based on a bridged bicyclic scaffold with selenocyano (SeCN) side chains. These compounds displayed potent ERα degradation and tubulin depolymerization activity. Among them, compounds 35s and 35t exhibited the most promising antiproliferative and ERα degradation activity in multiple ERα⁺ BC cell lines bearing either wild-type or mutant ERα. Meanwhile, compounds 35s and 35t disrupted the microtubule network by restraining tubulin polymerization, evidenced by 35t inducing cell cycle arrest in the G2/M phase. In MCF-7 and LCC2 xenograft models, compounds 35s and 35t remarkably suppressed tumor growth without noticeable poisonousness. Finally, this study provided guidance for developing new dual-target antitumor drug candidates for the ERα⁺ BC therapy, especially for the resistant variant.

100 Deals associated with 35-t

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