Discovery of MDV6058 (PF-06952229), a selective and potent TGFβR1 inhibitor: Design, synthesis and optimization.
Basic Information
ID: ALA5223120
Journal: Bioorg Med Chem Lett
Title: Discovery of MDV6058 (PF-06952229), a selective and potent TGFβR1 inhibitor: Design, synthesis and optimization.
Authors: Pujala B, Ramachandran SA, Sonawane M, Kamble MM, Panpatil D, Adhikari S, Soni S, Subbareddy V, Shinde BU, Nayak AK, Bansal C, Gupta A, Mukherjee K, Agarwal AK, Guerrero J, Herrera FJ, Bernales S, Guha M, Chakravarty S, Pham SM, Rai R.
Abstract: Compound 1 is a potent TGF-β receptor type-1 (TGFβR1 or ALK5) inhibitor but is metabolically unstable. A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described.
CiteXplore: 36089110
DOI: 10.1016/j.bmcl.2022.128979
Patent ID: ┄