2. Academic Validation
  3. Discovery of SARxxxx92, a pan-PIM kinase inhibitor, efficacious in a KG1 tumor model

Discovery of SARxxxx92, a pan-PIM kinase inhibitor, efficacious in a KG1 tumor model

  • Bioorg Med Chem Lett. 2020 Dec 1;30(23):127625. doi: 10.1016/j.bmcl.2020.127625.
Claude Barberis 1,  Paul Erdman 2,  Mark Czekaj 3,  Luke Fire 4,  James Pribish 3,  Elina Tserlin 5,  Sachin Maniar 3,  Joseph D Batchelor 3,  Jinyu Liu 3,  Vinod F Patel 6,  Andrew Hebert 7,  Mikhail Levit 7,  Anlai Wang 8,  Frank Sun 9,  Shih-Min A Huang 10
Affiliations

Affiliations

  • 1 IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States. Electronic address: claude.barberis2@sanofi.com.
  • 2 IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States; Present address: AbbVie, 100 Abbott Park Road, Abbott Park, IL 60064-3500, United States.
  • 3 IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States.
  • 4 IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States; Present address: Rakuten Medical, 11080 Roselle St, San Diego, CA 92121, United States.
  • 5 Present address: Qiagen, 561 Virginia Road, Concord, MA 01742, United States.
  • 6 Present address: TME Therapeutics, 3 Mossy Lane, Acton, MA 01720, United States.
  • 7 Oncology Biochemistry, Sanofi, 270 Albany Street, Cambridge MA 02139, United States.
  • 8 Oncology Biology, Sanofi, 270 Albany Street, Cambridge MA 02139, United States.
  • 9 Oncology Pharmacology, Sanofi, 640 Memorial Drive, Cambridge MA 02139, United States.
  • 10 Oncology Biology, Sanofi, 270 Albany Street, Cambridge MA 02139, United States; Present address: Bristol-Myers Squibb, 3551 Lawrenceville Princeton, Lawrence Township, NJ 08648, United States.
PMID: 33096160 DOI: 10.1016/j.bmcl.2020.127625
Abstract

N-substituted azaindoles were discovered as potent pan-PIM inhibitors. Lead optimization, guided by structure and focused on physico-chemical properties allowed us to solve inherent hERG and permeability liabilities, and provided compound 27, which subsequently impacted KG-1 tumor growth in a mouse model.

Keywords

AML; Cancer; Lead; PK/PD; Pan-PIM kinases; Tumor growth inhibition.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-142656
    Pim Inhibitor
    Pim