3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors
Апстракт
Rho-associated coiled-coil kinases (ROCKs) are involved in essential
cellular functions such as adhesion, contraction, motility, proliferation, and cell
survival/apoptosis. Four ROCK inhibitors have already been approved by the FDA and
are used to treat glaucoma (ripasudil and netarsudil), cerebral vasospasm (fasudil), and
graft-versus-host disease (belumosudil). Recent studies have focused on exploring the
role of ROCK kinase inhibitors in cancer treatment and the development of new ROCK
inhibitors. The main objective of this study was to identify critical structural features
relevant to the inhibition of ROCK1 using a ligand-based 3D-QSAR (3D quantitative
structure-activity relationship) method. The 3D-QSAR model for ROCK1 was created
and validated using internal and external validation parameters (R2, Q2, R2pred, rm2, r/2m, 𝑟���������𝑚���������
2̅̅̅
and ∆r2m). The main structural features that correlate with the inhibition of ROCK1 were
identified (e.g., heterocycle wi...th hydrogen donor group like nitrogen atom) and further
structural modifications of the ROCK1 inhibitors that contribute to increased activity
were proposed (removal of the amino group of the oxadiazole, modification of the
substituents of the phenyl ring).
Кључне речи:
ROCK / cancer / 3D-QSAR / designИзвор:
2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS, 2023, 1584-1588Издавач:
- Institute for Information Technologies, University of Kragujevac, Serbia
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
Напомена:
- 2nd International Conference on Chemo and Bioinformatics, September 28-29, 2023. Kragujevac, Serbia
Институција/група
PharmacyTY - CONF AU - Beljkaš, Milan AU - Rebić, Jelena AU - Radan, Milica AU - Đikić, Teodora AU - Oljačić, Slavica AU - Nikolić, Katarina PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5043 AB - Rho-associated coiled-coil kinases (ROCKs) are involved in essential cellular functions such as adhesion, contraction, motility, proliferation, and cell survival/apoptosis. Four ROCK inhibitors have already been approved by the FDA and are used to treat glaucoma (ripasudil and netarsudil), cerebral vasospasm (fasudil), and graft-versus-host disease (belumosudil). Recent studies have focused on exploring the role of ROCK kinase inhibitors in cancer treatment and the development of new ROCK inhibitors. The main objective of this study was to identify critical structural features relevant to the inhibition of ROCK1 using a ligand-based 3D-QSAR (3D quantitative structure-activity relationship) method. The 3D-QSAR model for ROCK1 was created and validated using internal and external validation parameters (R2, Q2, R2pred, rm2, r/2m, 𝑟���������𝑚��������� 2̅̅̅ and ∆r2m). The main structural features that correlate with the inhibition of ROCK1 were identified (e.g., heterocycle with hydrogen donor group like nitrogen atom) and further structural modifications of the ROCK1 inhibitors that contribute to increased activity were proposed (removal of the amino group of the oxadiazole, modification of the substituents of the phenyl ring). PB - Institute for Information Technologies, University of Kragujevac, Serbia C3 - 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS T1 - 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors SP - 1584 EP - 1588 DO - 10.46793/ICCBI23.584B ER -
@conference{ author = "Beljkaš, Milan and Rebić, Jelena and Radan, Milica and Đikić, Teodora and Oljačić, Slavica and Nikolić, Katarina", year = "2023", abstract = "Rho-associated coiled-coil kinases (ROCKs) are involved in essential cellular functions such as adhesion, contraction, motility, proliferation, and cell survival/apoptosis. Four ROCK inhibitors have already been approved by the FDA and are used to treat glaucoma (ripasudil and netarsudil), cerebral vasospasm (fasudil), and graft-versus-host disease (belumosudil). Recent studies have focused on exploring the role of ROCK kinase inhibitors in cancer treatment and the development of new ROCK inhibitors. The main objective of this study was to identify critical structural features relevant to the inhibition of ROCK1 using a ligand-based 3D-QSAR (3D quantitative structure-activity relationship) method. The 3D-QSAR model for ROCK1 was created and validated using internal and external validation parameters (R2, Q2, R2pred, rm2, r/2m, 𝑟���������𝑚��������� 2̅̅̅ and ∆r2m). The main structural features that correlate with the inhibition of ROCK1 were identified (e.g., heterocycle with hydrogen donor group like nitrogen atom) and further structural modifications of the ROCK1 inhibitors that contribute to increased activity were proposed (removal of the amino group of the oxadiazole, modification of the substituents of the phenyl ring).", publisher = "Institute for Information Technologies, University of Kragujevac, Serbia", journal = "2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS", title = "3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors", pages = "1584-1588", doi = "10.46793/ICCBI23.584B" }
Beljkaš, M., Rebić, J., Radan, M., Đikić, T., Oljačić, S.,& Nikolić, K.. (2023). 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS Institute for Information Technologies, University of Kragujevac, Serbia., 1584-1588. https://doi.org/10.46793/ICCBI23.584B
Beljkaš M, Rebić J, Radan M, Đikić T, Oljačić S, Nikolić K. 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS. 2023;:1584-1588. doi:10.46793/ICCBI23.584B .
Beljkaš, Milan, Rebić, Jelena, Radan, Milica, Đikić, Teodora, Oljačić, Slavica, Nikolić, Katarina, "3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors" in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS (2023):1584-1588, https://doi.org/10.46793/ICCBI23.584B . .