2. Academic Validation
  3. Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

  • Bioorg Med Chem Lett. 2012 Jul 1;22(13):4377-85. doi: 10.1016/j.bmcl.2012.04.131.
D Vijay Kumar 1,  Christophe Hoarau,  Matthew Bursavich,  Paul Slattum,  David Gerrish,  Kraig Yager,  Michael Saunders,  Mark Shenderovich,  Bruce L Roth,  Rena McKinnon,  Ashley Chan,  Daniel M Cimbora,  Chad Bradford,  Leslie Reeves,  Scott Patton,  Damon I Papac,  Brandi L Williams,  Robert O Carlson
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Myrexis Inc., 305 Chipeta Way, Salt Lake City, UT 84108, USA. dvijayku@hotmail.com
PMID: 22632936 DOI: 10.1016/j.bmcl.2012.04.131
Abstract

Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse.

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