2. Academic Validation
  3. The discovery of novel benzothiazinones as highly selective non-ATP competitive glycogen synthase kinase 3β inhibitors for the treatment of ovarian cancer

The discovery of novel benzothiazinones as highly selective non-ATP competitive glycogen synthase kinase 3β inhibitors for the treatment of ovarian cancer

  • Eur J Med Chem. 2017 Jul 28;135:370-381. doi: 10.1016/j.ejmech.2017.04.039.
Yang Gao 1,  De-Yong Ye 2,  Wei-Cheng Zhou 3,  Yong Chu 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China; State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives, State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address: [email protected].
  • 3 State Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives, State Institute of Pharmaceutical Industry, Shanghai, 201203, China. Electronic address: [email protected].
  • 4 Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address: [email protected].
PMID: 28460311 DOI: 10.1016/j.ejmech.2017.04.039
Abstract

Glycogen synthase kinase 3β (GSK 3β) is a highly conserved serine/threonine kinase, and its roles in Cancer remain controversial. Cumulative evidence supported that GSK 3β inhibitors could suppress ovarian Cancer (OC) development in vitro and made a new direction for ovarian Cancer treatment. Here, we reported a series of novel substituted benzothiazinones as non-ATP competitive inhibitors of GSK 3β. Further studies showed that most of them had antiproliferative activities in ovarian Cancer cell lines in vitro. As the most promising candidate of them, compound 20g induced cells Apoptosis, arrested the cell cycle at the G1 phase in the A2780 cell line and showed moderate suppression efficacy in a female BALB/C nude mice model. All of the results demonstrated that compound 20g, as the first reported non-ATP competitive small molecule inhibitor of GSK 3β with suppression efficacy on ovarian Cancer both in vitro and in vivo, might represent a potential candidate for the treatment of OC.

Keywords

Antiproliferative activities; Benzothiazinones; Glycogen synthase kinase 3β; Non-ATP competitive inhibitors; Ovarian cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-11012
    99.81%, GSK-3 Inhibitor