Delving into the Latest Updates on MRTX-9768 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

MTA-PRMT5

Action

inhibitors

Mechanism

MTA-PRMT5 inhibitors(MTA-Cooperative PRMT5 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Mirati Therapeutics, Inc.

Active Organization

Mirati Therapeutics, Inc.

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC24H17FN6O

InChIKeyBPTYWAYMKBEXES-UHFFFAOYSA-N

CAS Registry2629314-68-5

Author: Rahbaek, Lisa ; Wang, Xiaolun ; Kobayashi, Masakazu ; Jean-Baptiste, Ronald ; Burns, Aaron C. ; Kulyk, Svitlana ; Lawson, J. David ; Bobinski, Thomas P. ; Ivetac, Anthony ; Ketcham, John M. ; Marx, Matthew A. ; Engstrom, Lars D. ; Smith, Christopher R. ; Waters, Laura M. ; Briere, David M. ; Moya, Krystal ; Kuehler, Jon ; Christensen, James G. ; Olson, Peter ; Clarine, Jeffery ; Gunn, Robin J. ; Thomas, Nicole C. ; Aranda, Ruth

The PRMT5•MTA complex has recently emerged as a new synthetically lethal drug target for the treatment of MTAP-deleted cancers. Here, we report the discovery of development candidate MRTX1719. MRTX1719 is a potent and selective binder to the PRMT5•MTA complex and selectively inhibits PRMT5 activity in MTAP-deleted cells compared to MTAP-wild-type cells. Daily oral administration of MRTX1719 to tumor xenograft-bearing mice demonstrated dose-dependent inhibition of PRMT5-dependent symmetric dimethylarginine protein modification in MTAP-deleted tumors that correlated with antitumor activity. A 4-(aminomethyl)phthalazin-1(2H)-one hit was identified through a fragment-based screen, followed by X-ray crystallography, to confirm binding to the PRMT5•MTA complex. Fragment growth supported by structural insights from X-ray crystallography coupled with optimization of pharmacokinetic properties aided the discovery of development candidate MRTX1719.

100 Deals associated with MRTX-9768

Login to view more data