Delving into the Latest Updates on CAS-12290-201 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

VCPIP1

Action

inhibitors

Mechanism

VCPIP1 inhibitors(valosin containing protein interacting protein 1 inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Harvard Medical School

Active Organization

Harvard Medical School

Inactive Organization-

License Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC14H13ClFN3O2

InChIKeyVGBNJNGMPKJSPC-UHFFFAOYSA-N

CAS Registry-

Author: Dolen, Emma K ; Girardi, Nicholas M ; Chan, Wai Cheung ; Liu, Xiaoxi ; Magin, Robert S ; Hu, Wanyi ; Varca, Anthony C ; Buhrlage, Sara J ; Marto, Jarrod A ; Hu, Bin ; Ficarro, Scott B ; Jaen Maisonet, Isabella ; DaSilva, Ethan ; Tarazona Guzman, Maria I ; Ayala, Anthony X ; Starnbach, Cara A ; Bratt, Ariana S ; Felix, Alejandra ; Schauer, Nathan J ; Adelmant, Guillaume

AbstractDeubiquitinating enzymes (DUBs) are an emerging drug target class of ~100 proteases that cleave ubiquitin from protein substrates to regulate many cellular processes. A lack of selective chemical probes impedes pharmacologic interrogation of this important gene family. DUBs engage their cognate ligands through a myriad of interactions. We embrace this structural complexity to tailor a chemical diversification strategy for a DUB-focused covalent library. Pairing our library with activity-based protein profiling as a high-density primary screen, we identify selective hits against 23 endogenous DUBs spanning four subfamilies. Optimization of an azetidine hit yields a probe for the understudied DUB VCPIP1 with nanomolar potency and in-family selectivity. Our success in identifying good chemical starting points as well as structure-activity relationships across the gene family from a modest but purpose-build library challenges current paradigms that emphasize ultrahigh throughput in vitro or virtual screens against an ever-increasing scope of chemical space.

100 Deals associated with CAS-12290-201

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