Delving into the Latest Updates on PDHK1/2 Inhibitor(Roche) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

PDHK1 x PDHK2

Action

inhibitors

Mechanism

PDHK1 inhibitors(pyruvate dehydrogenase kinase 1 inhibitors), PDHK2 inhibitors(pyruvate dehydrogenase kinase 2 inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Roche Holding AGF. Hoffmann-La Roche Ltd.

Active Organization

Roche Holding AGF. Hoffmann-La Roche Ltd.

Inactive Organization-

License Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Author: Xu, Hongtao ; Ding, Dong ; Xu, Bruce ; Dey, Fabian ; Zhai, Guanglei ; Huang, Xinyi ; Wu, Waikong ; Casagrande, Fabio ; Han, Li ; Wu, Yao ; Roth, Doris ; Westwood, Paul ; Li, Chiho ; Schäfer, Ramona ; Ma, Tiantian ; Miao, Kun ; Zhao, Dan ; Strebel, Quentin ; Xia, Guliang ; Reutlinger, Michael ; Lin, Zhaohu ; Wichert, Moreno ; Zhao, Jie ; Han, Xingchun ; Chen, Shuai ; Zhang, Tong ; Heer, Dominik ; Zou, Ge ; Lassen, Kara ; Zhu, Wei ; Tian, Xiaojun ; Liang, Chungen ; Urich, Eduard ; Shen, Hong C ; Yun, Hongying ; Hilbert, Manuel ; Yang, June

Multiple screening approaches were carried out to identify novel chemistry starting for Pyruvate Dehydrogenase Kinases (PDHKs) inhibitors. Through hit triaging efforts and structure-based optimization, two series of ATP competitive inhibitors with single digit nanomolar enzymatic potency for PDHK1/2 and around 10-100-fold selectivity over PDHK4/3 were discovered. Approach of covalent inhibitor was explored to successfully improve the cellular target engagement to single digit micromolar range.

100 Deals associated with PDHK1/2 Inhibitor(Roche)

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