Delving into the Latest Updates on DC-U43-10 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

USP8

Action

inhibitors

Mechanism

USP8 inhibitors(ubiquitin specific peptidase 8 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

Shanghai Institute of Materia Medica Chinese Academy of Sci

Active Organization-

Inactive Organization

Shanghai Institute of Materia Medica Chinese Academy of Sci

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

USP8, one member of deubiquitinating enzymes (DUBs) families, maintains the ubiquitination level of EGFR and regulates the downstream signaling pathways. The deregulation of USP8 has been implicated in many human diseases, especially in cancer. Therefore, USP8 has been identified as a promising target for drug design. Herein, via high throughput screening based on Ubiquitin-rhodamine-110 (Ubiquitin-Rho-110) fluorometric activity assay, we discovered a novel inhibitor DC-U43. By structure optimization, DC-U43-10 reached a half-maximal inhibitory concentration (IC₅₀) value of 2.6 ± 1.1 μM and exhibited 10-fold selectivity against USP7. The binding between DC-U43-10 and USP8 was validated by surface plasmon resonance (SPR) assay with a K_D value of 10.5 ± 3.7 μM. It also inhibited the colony formation of H1975 cells. Hence, DC-U43-10 represents a kind of USP8 inhibitors with novel scaffold and has broad prospects for being a probe for USP8-related academic and clinical research.

100 Deals associated with DC-U43-10

Login to view more data