Computer-aided CDK6 inhibitor compounds lead compounds preliminary design and determination of activity.docVIP

 PAGE \* MERGEFORMAT 9 Computer-aided CDK6 inhibitor compounds lead compounds preliminary design and determination of activity Authors: Guo-Guang, GUO Kun-yuan, Shang-chuan Keywords: computer-aided drug design Computerassisted primary design of lead compounds of CDK6 inhibitors and determination of their bioactivity 【Abstract】 AIM: To primarily design the lead compounds of CDK16 inhibitors based on CDK6 structure and to test their bioactivity. METHODS: Using LigBuilderv1.2 [a kind of computerassisted drug design (CADD) program], we tried to design new lead compunds of CDK6 inhibitors by method of de novo design and according to Lipinski rule, and test their IC50 by MTT assay. RESULTS: We got the structures of 50 new chemical compounds as the lead compounds for further drug filtering, and 3 of 8 compunds we synthesized successfully had a bioactivity between 220 and 310 μmol / L. CONCLUSION: The new compunds have some inhibitory activity and the efficiency of finding lead compounds can be improved with the help of CADD. 【Keywords】 CADD; CDK6 inhibitor; IC50 【Abstract】 Objective: Preliminary design of CDK6 inhibitor lead compounds and to determine compound activity. Methods: The use of computer-aided drug design (CADD) programs LigBuilderv1.2, based on Lipinski rules, using the design from scratch, fragment growth by way of the Linux operating system, Next, design a new CDK6 inhibitor compounds; MTT determination of compounds IC50. RESULTS: 50 kinds of compounds and has successfully synthesized eight kinds, after determination of which there are three kinds of activity (IC50 in 220 ~ 310 μmol / L Room). Conclusion: new CDK6 inhibitor compounds have a certain inhibitory activity, CADD can greatly enhance the efficiency of lead compound discovery and speed up the step on behalf of New Drug Research. Keywords: computer-aided drug design; CDK6 inhibitor; IC50 0 Introduction According to cancer stem cell theory [1