1. Academic Validation
  2. Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma

Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma

  • J Med Chem. 2019 Feb 28;62(4):2140-2153. doi: 10.1021/acs.jmedchem.8b01857.
Xiaojing Wang 1 Wesley Blackaby 2 Vivienne Allen 2 Grace Ka Yan Chan 1 Jae H Chang 1 Po-Chang Chiang 1 Coura Diène 2 Jason Drummond 1 Steven Do 1 Eric Fan 1 Eric B Harstad 1 Alastair Hodges 2 Huiyong Hu 1 Wei Jia 1 William Kofie 2 Aleksandr Kolesnikov 1 Joseph P Lyssikatos 1 Justin Ly 1 Mizio Matteucci 2 John G Moffat 1 Veerendra Munugalavadla 1 Jeremy Murray 1 David Nash 2 Cameron L Noland 1 Geoff Del Rosario 1 Leanne Ross 1 Craig Rouse 2 Andrew Sharpe 2 Dionysos Slaga 1 Minghua Sun 1 Vickie Tsui 1 Heidi Wallweber 1 Shang-Fan Yu 1 Allen J Ebens 1
Affiliations

Affiliations

  • 1 Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States.
  • 2 Charles River Discovery Research Services UK Limited (formerly BioFocus), Chesterford Research Park , Saffron Walden , Essex CB10 1XL , United Kingdom.
Abstract

Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16976
    99.87%, Pim Inhibitor
    Pim