%0 Journal Article %1 Tanaka2011LEIFragmentsEH %A Tanaka, Daisuke %A Tsuda, Yusuke %A Shiyama, Takaaki %A Nishimura, Tamiki %A Chiyo, Naoki %A Tominaga, Yukio %A Sawada, Nobuyuki %A Mimoto, Tsutomu %A Kusunose, Naoto %D 2011 %J Journal of Medicinal Chemistry %K fragment-based-screening lead-identification ligand-efficiency sEH soluble-epoxide-hydrolase %N 3 %P 851-857 %R 10.1021/jm101273e %T A Practical Use of Ligand Efficiency Indices Out of the Fragment-Based Approach: Ligand Efficiency-Guided Lead Identification of Soluble Epoxide Hydrolase Inhibitors %U http://dx.doi.org/10.1021/jm101273e %V 54 %X Ligand efficiency is frequently used to evaluate fragment compounds in fragment-based drug discovery. We applied ligand efficiency indices in a conventional virtual screening-initiated lead generation study of soluble epoxide hydrolase inhibitors. From a considerable number of screening hits, we carefully selected a compound exhibiting relatively weak inhibitory activity but high ligand efficiency. This ligand efficiency-guided selection could reveal compounds possessing preferable lead-like characteristics in terms of molecular size and lipophilicity. The following hit-to-lead medicinal chemistry campaign successfully led to a more potent, ADMET-clean, lead-like compound preserving high ligand efficiency. Retrospective analyses, including consideration of the more recently proposed indices of ligand efficiency, shed light on the validity of our hit triage and hit-to-lead studies. The present work proposes a practical methodology for lead generation using the concept of ligand efficiency.

@article{Tanaka2011LEIFragmentsEH, abstract = { Ligand efficiency is frequently used to evaluate fragment compounds in fragment-based drug discovery. We applied ligand efficiency indices in a conventional virtual screening-initiated lead generation study of soluble epoxide hydrolase inhibitors. From a considerable number of screening hits, we carefully selected a compound exhibiting relatively weak inhibitory activity but high ligand efficiency. This ligand efficiency-guided selection could reveal compounds possessing preferable lead-like characteristics in terms of molecular size and lipophilicity. The following hit-to-lead medicinal chemistry campaign successfully led to a more potent, ADMET-clean, lead-like compound preserving high ligand efficiency. Retrospective analyses, including consideration of the more recently proposed indices of ligand efficiency, shed light on the validity of our hit triage and hit-to-lead studies. The present work proposes a practical methodology for lead generation using the concept of ligand efficiency. }, added-at = {2017-03-06T02:47:40.000+0100}, author = {Tanaka, Daisuke and Tsuda, Yusuke and Shiyama, Takaaki and Nishimura, Tamiki and Chiyo, Naoki and Tominaga, Yukio and Sawada, Nobuyuki and Mimoto, Tsutomu and Kusunose, Naoto}, biburl = {https://www.bibsonomy.org/bibtex/22f68d437e753fe3f6f01a74ff00a480e/salotz}, description = {A Practical Use of Ligand Efficiency Indices Out of the Fragment-Based Approach: Ligand Efficiency-Guided Lead Identification of Soluble Epoxide Hydrolase Inhibitors - Journal of Medicinal Chemistry (ACS Publications)}, doi = {10.1021/jm101273e}, eprint = {http://dx.doi.org/10.1021/jm101273e}, interhash = {59c57a37a1954663ea6ed242ca769da6}, intrahash = {2f68d437e753fe3f6f01a74ff00a480e}, journal = {Journal of Medicinal Chemistry}, keywords = {fragment-based-screening lead-identification ligand-efficiency sEH soluble-epoxide-hydrolase}, note = {PMID: 21192659}, number = 3, pages = {851-857}, timestamp = {2017-03-06T02:47:40.000+0100}, title = {A Practical Use of Ligand Efficiency Indices Out of the Fragment-Based Approach: Ligand Efficiency-Guided Lead Identification of Soluble Epoxide Hydrolase Inhibitors}, url = {http://dx.doi.org/10.1021/jm101273e}, volume = 54, year = 2011 }