2. Academic Validation
  3. Discovery of a Series of 5,11-Dihydro-6 H-benzo[ e]pyrimido[5,4- b][1,4]diazepin-6-ones as Selective PI3K-δ/γ Inhibitors

Discovery of a Series of 5,11-Dihydro-6 H-benzo[ e]pyrimido[5,4- b][1,4]diazepin-6-ones as Selective PI3K-δ/γ Inhibitors

  • ACS Med Chem Lett. 2016 Aug 2;7(10):908-912. doi: 10.1021/acsmedchemlett.6b00209.
Fleur M Ferguson 1,  Jing Ni 1,  Tinghu Zhang 1,  Bethany Tesar 2,  Taebo Sim 3,  Nam Doo Kim 4,  Xianming Deng 1,  Jennifer R Brown 2,  Jean J Zhao 1,  Nathanael S Gray 1
Affiliations

Affiliations

  • 1 Department of Cancer Biology, Dana-Farber Cancer Institute , Boston, Massachusetts 02215, United States.
  • 2 Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, United States; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, United States.
  • 3 Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea.
  • 4 Daegu-Gyeongbuk Medical Innovation Foundation , Daegu 41061, Republic of Korea.
PMID: 27774127 DOI: 10.1021/acsmedchemlett.6b00209
Abstract

Dual inhibition of PI3K-δ and PI3K-γ is an established therapeutic strategy for treatment of hematological malignancies. Reported molecules targeting PI3K-δ/γ selectively are chemically similar and based upon isoquinolin-1(2H)-one or quinazolin-4(3H)-one scaffolds. Here we report a chemically distinct series of potent, selective PI3K-δ/γ inhibitors based on a 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one scaffold with comparable biochemical potency and cellular effects on PI3K signaling. We envisage these molecules will provide useful leads for development of next-generation PI3K-δ/γ targeting therapeutics.

Keywords

PI3K-γ; PI3K-δ; kinase inhibitor; p110-γ; p110-δ; phosphatidylinositol-4,5-bisphosphate 3-kinase-delta.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-144993
    99.85%, PI3Kδ/γ Inhibitor