- Title of Paper:SAR study of 1,2-benzisothiazole dioxide compounds that agonize HIF-2 stabilization and EPO production.
- Journal:Bioorganic & Medicinal Chemistry
- Key Words:Agonist; Benzisothiazole; EPO; HIF-2; SAR.
- Summary:Benzisothiazole dioxide compound was reported to agonize HIF-2 stabilization and improve EPO production, thus conceiving a potential strategy to treat disease with chronic hypoxia exemplified by renal anemia. Herein, on the bases of multiple molecular and cellular assays, a series of benzisothiazole derivatives have been synthesized and their structure-activity relationship was evaluated. The SAR and molecular docking studies have revealed the structural insights on the rational design of HIF-2 agonist and discovered a more potential 5-bromine substituted analogue, which showed 2-4 times improvement of HIF-2 downstream gene transcriptions, including EPO production. The present results suggest the therapeutic potential of the compounds for diseases related to EPO insufficiency.
- Volume:77
- Page Number:117041
- DOI Number:10.1016/j.bmc.2022.117041.
- Translation or Not:No
- Date of Publication:2023-01
- Included Journals:SCI
- Release Time:2023-01-01
Summary:Benzisothiazole dioxide compound was reported to agonize HIF-2 stabilization and improve EPO production, thus conceiving a potential strategy to treat disease with chronic hypoxia exemplified by renal anemia. Herein, on the bases of multiple molecular and cellular assays, a series of benzisothiazole derivatives have been synthesized and their structure-activity relationship was evaluated. The SAR and molecular docking studies have revealed the structural insights on the rational design of HIF-2 agonist and discovered a more potential 5-bromine substituted analogue, which showed 2-4 times improvement of HIF-2 downstream gene transcriptions, including EPO production. The present results suggest the therapeutic potential of the compounds for diseases related to EPO insufficiency.
MOBILE Version