A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors

  • Bioorg Med Chem Lett. 2016 May 15;26(10):2434-2437. doi: 10.1016/j.bmcl.2016.03.116.
Yinping Tian  1 ,  Jin Jin  1 ,  Congying Wang  1 ,  Wenhui Lv  1 ,  Xuewei Li  1 ,  Xiaona Che  1 ,  Yanchao Gong  1 ,  Yanjun Li  1 ,  Quanli Li  1 ,  Jingli Hou  2 ,  Peng G Wang  3 ,  Jie Shen  4
Affiliations
  • 1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China.
  • 2. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, People's Republic of China.
  • 3. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: [email protected].
  • 4. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: [email protected].
PMID: 27055940 DOI: 10.1016/j.bmcl.2016.03.116
Abstract

This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2μM in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works.

Keywords
HDAC11; Solid phase synthesis; Sub-milligram-synthesis; UV quantification; Unconjugated chromophore.