Delving into the Latest Updates on C3TD879 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

Mechanism

ACL inhibitors(ATP-citrate synthase inhibitors), CIT inhibitors(citron rho-interacting serine/threonine kinase inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Cleveland Clinic Lerner Research Institute

Active Organization

The Cleveland Clinic Foundation

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H28N4O

InChIKeyODOJVROSIRINJT-IBGZPJMESA-N

CAS Registry2850259-97-9

Citron kinase (CITK) is an AGC-family serine/threonine kinase that regulates cytokinesis. Despite knockdown experiments implicating CITK as an anticancer target, no selective CITK inhibitors exist. We transformed a previously reported kinase inhibitor with weak off-target CITK activity into a first-in-class CITK chemical probe, C3TD879. C3TD879 is a Type I kinase inhibitor which potently inhibits CITK catalytic activity (biochemical IC₅₀ = 12 nM), binds directly to full-length human CITK in cells (NanoBRET K_d < 10 nM), and demonstrates favorable DMPK properties for in vivo evaluation. We engineered exquisite selectivity for CITK (>17-fold versus 373 other human kinases), making C3TD879 the first chemical probe suitable for interrogating the complex biology of CITK. Our small-molecule CITK inhibitors could not phenocopy the effects of CITK knockdown in cell proliferation, cell cycle progression, or cytokinesis assays, providing preliminary evidence that the structural roles of CITK may be more important than its kinase activity.

100 Deals associated with C3TD879

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