1. Academic Validation
  2. Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL)

Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL)

  • J Med Chem. 2024 Nov 14;67(21):19234-19246. doi: 10.1021/acs.jmedchem.4c01659.
Rebecca A Gallego 1 Stephanie Scales 1 Chad Toledo 2 Marin Auth 2 Louise Bernier 1 Madeline Berry 1 Sonja Brun 2 Loanne Chung 1 Carl Davis 2 Wade Diehl 1 Klaus Dress 1 Koleen Eisele 2 Jeff Elleraas 1 Jason Ewanicki 1 Yvette Fobian 1 Samantha Greasley 1 Eric C Greenwald 2 Ted W Johnson 1 Penney Khamphavong 2 Jennifer Lafontaine 1 Jian Li 2 Angelica Linton 1 Michael Maestre 2 Nichol Miller 2 Anwar Murtaza 2 Ryan L Patman 1 Casey L Quinlan 2 Dana J Ramms 2 Paul Richardson 1 Neal Sach 1 Romelia Salomon-Ferrer 1 Francisco Silva 1 Sergei Timofeevski 2 Phuong Tran 1 Michelle Tran-Dubé 1 Fen Wang 1 Wei Wang 1 Martin Wythes 1 Shouliang Yang 1 Aihua Zou 2 Todd VanArsdale 2 Indrawan McAlpine 1
Affiliations

Affiliations

  • 1 Oncology Medicinal Chemistry, Pfizer Worldwide Research and Development, 10770 Science Center Drive, La Jolla, California 92121, United States.
  • 2 Oncology Research Unit, Pfizer Worldwide Research and Development, 10770 Science Center Drive, La Jolla, California 92121, United States.
Abstract

By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis. The resulting advanced lead compounds enabled a tumor growth inhibition study which was pivotal in assessing the potential value of MASTL as an oncology therapeutic target.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-156715
    99.54%, MASTL Inhibitor