2. Academic Validation
  3. 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.
PMID: 30715878 DOI: 10.1021/acs.jmedchem.8b01857
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
    99.77%, Pim Inhibitor
    Pim