1. Academic Validation
  2. Potent and novel 11β-HSD1 inhibitors identified from shape and docking based virtual screening

Potent and novel 11β-HSD1 inhibitors identified from shape and docking based virtual screening

  • Bioorg Med Chem Lett. 2011 Oct 1;21(19):5739-44. doi: 10.1016/j.bmcl.2011.08.019.
Guangxin Xia 1 Mengzhu Xue Lin Liu Jianxin Yu Haiyan Liu Ping Li Jianfa Wang Yanlian Li Bing Xiong Jingkang Shen
Affiliations

Affiliation

  • 1 Central Research Institute, Shanghai Pharmaceutical Holding Co. Ltd, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
Abstract

Several potent and novel 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors were discovered from in silico screening the commercially available Maybridge database. Among them, seven hit compounds showed good affinity, with IC(50) values lower than 100 nM and the best one 3.7 nM. To select the lead for further optimization, computational ADME/T prediction, the CYP3A4 inhibition and 11β-HSD1 over 11β-HSD2 selectivity test were also performed. Taking all of the above factors into consideration, two promising compounds were selected as lead structures for further development. The employed hierarchical virtual screening protocol not only demonstrates its efficiency, but also provides novel and selective compounds for developing 11β-HSD1 inhibitors to protect against metabolic syndrome.

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