In silico screening of small molecule compounds for substitution of neutralizing antibodies.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670129
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kyushu University
• Principal Investigator: OIKE Masahioro 九州大学, 医学(系)研究科(研究院), 准教授 (70271103)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: インシリコスクリーニング / TGFβ1 / 阻害薬 / 上皮間葉移行

Outline of Final Research Achievements

This study aimed to develop small molecular compounds that bind and suppress TGFβ1 protein. I set three binding sites on the surface of TGFβ1 protein, i.e., whole binding region to type II TGFβ receptor (TGFBR2), electrostatic pocket of TGFBR2 binding region, and allosteric electrostatic pocket outside the receptor binding regions. Then I calculated binding affinities of virtual small molecular compounds to these binding sites, and examined the effects of high affinity compounds on TGFβ1-induced epithelial-mesenchymal transition in A549 cells. The results were that compounds that had high binding affinity to allosteric site showed the highest possibility of inhibition. This study indicates that effects of TGFβ1 can be suppressed by small molecular compounds that allosterically affect binding of TGFβ1 to TGFBR2.

Free Research Field

薬理学