Structure-based drug design identifies novel LPA3 antagonists
Abstract
Compound 5 ([5-(3-nitrophenoxy)-1,3-dioxo-1,3-dihydro-2-isoindol-2-y1] acetic acid) was identified as a weak selective LPA3 antagonist (IC50 4504 nM) in a virtual screening effort to optimize a dual LPA2 and 3 antagonist. Structure-based drug design techniques were used to prioritize similarity search matches of compound 5. This strategy rapidly identified 10 novel antagonists. The two most efficacious compounds identified inhibit activation of the LPA3 receptor by 200 nM LPA with IC50 values of 752 nM and 299211M. These compounds additionally define changes to our previously reported pharmacophore that will improve its ability to identify more potent and selective LPA3 receptor antagonists. The results of the combined computational and experimental screening are reported. © 2009 Elsevier Ltd. All rights reserved.
Publication Title
Bioorganic and Medicinal Chemistry
Recommended Citation
Fells, J., Tsukahara, R., Liu, J., Tigyi, G., & Parrill, A. (2009). Structure-based drug design identifies novel LPA3 antagonists. Bioorganic and Medicinal Chemistry, 17 (21), 7457-7464. https://doi.org/10.1016/j.bmc.2009.09.022
