Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors
Апстракт
Overexpression of Rho-associated protein kinases has been associated with various
diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment.
However, some of them have been shown to have anti-tumor potential. The main objective of this
study was to develop novel ROCK1 inhibitors using the structure-based method, molecular
docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key
interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds
between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating
possible structural changes in the hinge region of studied compounds. On the other hand, the
lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising
approach for further structural modifications in order to design more effective ROCK1 inhibitors.
All the important interactions between the developed ROCK1 inhibitors and... the binding site
of the enzyme were established. They also showed acceptable pharmacokinetic properties and
could be further used for synthesis and evaluation by various biological assays.
Кључне речи:
molecular docking / ADME / design / ROCK1Извор:
2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS, 2023, 1589-1592Издавач:
- 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/123456789/5041 AB - Overexpression of Rho-associated protein kinases has been associated with various diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment. However, some of them have been shown to have anti-tumor potential. The main objective of this study was to develop novel ROCK1 inhibitors using the structure-based method, molecular docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating possible structural changes in the hinge region of studied compounds. On the other hand, the lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising approach for further structural modifications in order to design more effective ROCK1 inhibitors. All the important interactions between the developed ROCK1 inhibitors and the binding site of the enzyme were established. They also showed acceptable pharmacokinetic properties and could be further used for synthesis and evaluation by various biological assays. PB - Institute for Information Technologies, University of Kragujevac, Serbia C3 - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS T1 - Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors SP - 1589 EP - 1592 DO - 10.46793/ICCBI23.589B ER -
@conference{ author = "Beljkaš, Milan and Rebić, Jelena and Radan, Milica and Đikić, Teodora and Oljačić, Slavica and Nikolić, Katarina", year = "2023", abstract = "Overexpression of Rho-associated protein kinases has been associated with various diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment. However, some of them have been shown to have anti-tumor potential. The main objective of this study was to develop novel ROCK1 inhibitors using the structure-based method, molecular docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating possible structural changes in the hinge region of studied compounds. On the other hand, the lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising approach for further structural modifications in order to design more effective ROCK1 inhibitors. All the important interactions between the developed ROCK1 inhibitors and the binding site of the enzyme were established. They also showed acceptable pharmacokinetic properties and could be further used for synthesis and evaluation by various biological assays.", publisher = "Institute for Information Technologies, University of Kragujevac, Serbia", journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS", title = "Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors", pages = "1589-1592", doi = "10.46793/ICCBI23.589B" }
Beljkaš, M., Rebić, J., Radan, M., Đikić, T., Oljačić, S.,& Nikolić, K.. (2023). Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS Institute for Information Technologies, University of Kragujevac, Serbia., 1589-1592. https://doi.org/10.46793/ICCBI23.589B
Beljkaš M, Rebić J, Radan M, Đikić T, Oljačić S, Nikolić K. Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS. 2023;:1589-1592. doi:10.46793/ICCBI23.589B .
Beljkaš, Milan, Rebić, Jelena, Radan, Milica, Đikić, Teodora, Oljačić, Slavica, Nikolić, Katarina, "Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS (2023):1589-1592, https://doi.org/10.46793/ICCBI23.589B . .