Delving into the Latest Updates on WDR5/MYC inhibitors(Zhejiang University) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

WDR5 x c-Myc

Action

inhibitors

Mechanism

MYC inhibitors(Myc proto-oncogene protein inhibitors), WDR5 inhibitors(WD repeat-containing protein 5 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Zhejiang University

Active Organization

Zhejiang University

Inactive Organization-

License Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

MYC amplification is frequently observed in approximately 50% of human cancers, rendering it a highly desired anticancer target. Given the challenge of direct pharmacological inhibiting of MYC, impairing the interaction of MYC and its key cofactor WDR5 has been proposed as a promising strategy for MYC-driven cancer treatment. Herein, we report the discovery of 5-thiocyanatothiazol-2-amines that disrupt the WDR5-MYC interaction. Hit fragments were initially identified in a fluorescence polarization (FP)-based screening of an in-house library, and structural-activity relationship exploration resulted in the lead compounds 4m and 4o with potent inhibitory activities on WDR5-MYC interaction (K _i = 2.4 μM for 4m; K _i = 1.0 μM for 4o). These compounds were further validated via differential scanning fluorimetry (DSF) and coimmunoprecipitation (Co-IP). Moreover, 4m and 4o exhibited good cellular activities with the IC₅₀ values at the micromolar level (IC₅₀ = 0.71-7.40 μM) against multiple MYC-driven cancer cell lines. Our findings afforded a potential small molecule blocking the WDR5-MYC interaction.

100 Deals associated with WDR5/MYC inhibitors(Zhejiang University)

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