424
Views
9
CrossRef citations to date
0
Altmetric
Research Articles

Pharmacophore-guided fragment-based design of novel mammalian target of rapamycin inhibitors: extra precision docking, fingerprint-based 2D and atom-based 3D-QSAR modelling

, , , &
Pages 1155-1173 | Received 04 Dec 2019, Accepted 03 Feb 2020, Published online: 19 Feb 2020

References

  • Anju, C. P., Subhramanian, S., Sizochenko, N., Melge, A. R., Leszczynski, J., & Mohan, C. G. (2019). Multiple e-Pharmacophore modeling to identify a single molecule that could target both streptomycin and paromomycin binding sites for 30S ribosomal subunit inhibition. Journal of Biomolecular Structure and Dynamics, 37(6), 1582–1596. doi:10.1080/07391102.2018.1462731
  • Campbell, S. F. (2000). Science, art and drug discovery: A personal perspective. Clinical Science, 99(4), 255–260. doi:10.1042/cs0990255
  • Carew, J. S., Kelly, K. R., & Nawrocki, S. T. (2011). Mechanisms of mTOR inhibitor resistance in cancer therapy. Targeted Oncology, 6(1), 17–27. doi:10.1007/s11523-011-0167-8
  • Congreve, M., Murray, C. W., & Blundell, T. L. (2005). Structural biology and drug discovery. Drug Discovery Today, 10(13), 895–907. doi:10.1016/S1359-644(05)03484-7
  • D’Angelo, N. D., Kim, T.-S., Andrews, K., Booker, S. K., Caenepeel, S., Chen, K., … Norman, M. H. (2011). Discovery and optimization of a series of benzothiazole phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors. Journal of Medicinal Chemistry, 54(6), 1789–1811. doi:10.1021/jm1014605
  • Dixon, S. L., Smondyrev, A. M., Knoll, E. H., Rao, S. N., Shaw, D. E., & Friesner, R. A. (2006). PHASE: A new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results. Journal of Computer-Aided Molecular Design, 20(10–11), 647–671. doi:10.1007/s10822-006-9087-6
  • Duan, J., Dixon, S. L., Lowrie, J. F., & Sherman, W. (2010). Analysis and comparison of 2D fingerprints: Insights into database screening performance using eight fingerprint methods. Journal of Molecular Graphics and Modelling, 29(2), 157–170. doi:10.1016/j.jmgm.2010.05.008
  • Erlanson, D. A., Fesik, S. W., Hubbard, R. E., Jahnke, W., & Jhoti, H. (2016). Twenty years on: The impact of fragments on drug discovery. Nature Reviews Drug Discovery, 15(9), 605–619. doi:10.1038/nrd.2016.109
  • Fragment Libraries | FCH Group. (n.d.). Retrieved from http://fchgroup.net/fragment-libraries.php
  • Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., … Mainz, D. T. (2006). Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein − ligand complexes. Journal of Medicinal Chemistry, 49(21), 6177–6196. doi:10.1021/jm051256o
  • Hardy, L. W., & Malikayil, A. (2003). The impact of structure-guided drug design on clinical agents. Current Drug Discovery, 3, 15–20.
  • Ito, J. I., Tabei, Y., Shimizu, K., Tsuda, K., & Tomii, K. (2012). PoSSuM: A database of similar protein-ligand binding and putative pockets. Nucleic Acids Research, 40(D1), D541–D548. doi:10.1093/nar/gkr1130
  • Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004). Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nature Cell Biology, 6(11), 1122–1128. doi:10.1038/ncb1183
  • Jana, S., Ganeshpurkar, A., & Singh, S. K. (2018). Multiple 3D-QSAR modeling, e-pharmacophore, molecular docking, and in vitro study to explore novel AChE inhibitors. RSC Advances, 8(69), 39477–39495. doi:10.1039/c8ra08198k
  • Jhanwar-Uniyal, M., Wainwright, J. V., Mohan, A. L., Tobias, M. E., Murali, R., Gandhi, C. D., & Schmidt, M. H. (2019). Diverse signaling mechanisms of mTOR complexes: MTORC1 and mTORC2 in forming a formidable relationship. Advances in Biological Regulation, 72(2), 51–62. doi:10.1016/j.jbior.2019.03.003
  • Kist, R., & Caceres, R. A. (2017). New potential inhibitors of mTOR: A computational investigation integrating molecular docking, virtual screening and molecular dynamics simulation. Journal of Biomolecular Structure and Dynamics, 35(16), 3555–3568. doi:10.1080/07391102.2016.1262279
  • Kist, R., Timmers, L. F. S. M., & Caceres, R. A. (2018). Searching for potential mTOR inhibitors: Ligand-based drug design, docking and molecular dynamics studies of rapamycin binding site. Journal of Molecular Graphics and Modelling, 80, 251–263. doi:10.1016/j.jmgm.2017.12.015
  • Kumar, A., Rathi, E., & Kini, S. G. (2019a). E-pharmacophore modelling, virtual screening, molecular dynamics simulations and in-silico ADME analysis for identification of potential E6 inhibitors against cervical cancer. Journal of Molecular Structure, 1189, 299–306. doi:10.1016/j.molstruc.2019.04.023
  • Kumar, A., Rathi, E., & Kini, S. G. (2019b). Identification of E6 inhibitors employing energetically optimized structure‐based pharmacophore modelling, ligand docking and molecular dynamics simulations studies. ChemistrySelect, 4(36), 10701–10708. doi:10.1002/slct.201902105
  • Kumar, A., Rathi, E., & Kini, S. G. (2019c). Identification of potential tumour-associated carbonic anhydrase isozyme IX inhibitors: Atom-based 3D-QSAR modelling, pharmacophore-based virtual screening and molecular docking studies. Journal of Biomolecular Structure and Dynamics, 38, 1–15. doi:10.1080/07391102.2019.1626285
  • Laplante, M., & Sabatini, D. M. (2012). MTOR signaling in growth control and disease. Cell, 149(2), 274–293. doi:10.1016/j.cell.2012.03.017
  • Lee, S.-Y., Lee, H., Lee, H.-K., Lee, S.-W., Ha, S. C., Kwon, T., … Rhee, H.-W. (2016). Proximity-directed labeling reveals a new rapamycin-induced heterodimer of FKBP25 and FRB in live cells. ACS Central Science, 2(8), 506–516. doi:10.1021/acscentsci.6b00137
  • Lv, X., Ma, X., & Hu, Y. (2013). Furthering the design and the discovery of small molecule ATP-competitive mTOR inhibitors as an effective cancer treatment. Expert Opinion on Drug Discovery, 8(8), 991–1012. doi:10.1517/17460441.2013.800479
  • Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221–234. doi:10.1007/s10822-013-9644-8
  • Maksoud, M. S., El-Gamal, M. I., Benhalilou, D. R., Ashraf, S., Mohammed, S. A., & Oh, C. H. (2019). Mechanistic/mammalian target of rapamycin: Recent pathological aspects and inhibitors. Medicinal Research Reviews, 39(2), 631–664. doi:10.1002/med.21535
  • Murray, C. W., & Rees, D. C. (2009). The rise of fragment-based drug discovery. Nature Chemistry, 1(3), 187–192. doi:10.1038/nchem.217
  • Ranjbar, S., Edraki, N., Khoshneviszadeh, M., Foroumadi, A., Miri, R., & Khoshneviszadeh, M. (2018). Design, synthesis, cytotoxicity evaluation and docking studies of 1,2,4-triazine derivatives bearing different arylidene-hydrazinyl moieties as potential mTOR inhibitors. Research in Pharmaceutical Sciences, 13(1), 1–11. doi:10.4103/1735-5362.220962
  • Rashid, M. M., Lee, H., & Jung, B. H. (2018). Metabolite identification and pharmacokinetic profiling of PP242, an ATP-competitive inhibitor of mTOR using ultra high-performance liquid chromatography and mass spectrometry. Journal of Chromatography B, 1072, 244–251. doi:10.1016/j.jchromb.2017.11.027
  • Rodrik-Outmezguine, V. S., Okaniwa, M., Yao, Z., Novotny, C. J., McWhirter, C., Banaji, A., … Shokat, K. M. (2016). Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature, 534(7606), 272–276. doi:10.1038/nature17963
  • Rosipal, R. (2003). Kernel partial least squares for nonlinear regression and discrimination. Neural Network World, 13(3), 291–300.
  • Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., … Sabatini, D. M. (2006). Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Molecular Cell, 22(2), 159–168. doi:10.1016/j.molcel.2006.03.029
  • Schenone, S., Brullo, C., Musumeci, F., Radi, M., & Botta, M. (2011). ATP-competitive inhibitors of mTOR: An update. Current Medicinal Chemistry, 18(20), 2995–3014. doi:10.2174/092986711796391651
  • Sehgal, S. N. (2003). Sirolimus: Its discovery, biological properties, and mechanism of action. Transplantation Proceedings, 35(3), S7–S14. doi:10.1016/S0041-1345(03)00211-2
  • Sharlow, E. R., Leimgruber, S., Lira, A., McConnell, M. J., Norambuena, A., Bloom, G. S., … Lazo, J. S. (2016). A small molecule screen exposes mTOR signaling pathway involvement in radiation-induced apoptosis. ACS Chemical Biology, 11(5), 1428–1437. doi:10.1021/acschembio.5b00909
  • Stahl, M., & Mauser, H. (2005). Database clustering with a combination of fingerprint and maximum common substructure methods. Journal of Chemical Information and Modeling, 45(3), 542–548. doi:10.1021/ci050011h
  • Takeda, T., Wang, Y., & Bryant, S. H. (2016). Structural insights of a PI3K/mTOR dual inhibitor with the morpholino-triazine scaffold. Journal of Computer-Aided Molecular Design, 30(4), 323–330. doi:10.1007/s10822-016-9905-4
  • Tripathy, S., Azam, M. A., Jupudi, S., & Sahu, S. K. (2018). Pharmacophore generation, atom-based 3D-QSAR, molecular docking and molecular dynamics simulation studies on benzamide analogues as FtsZ inhibitors. Journal of Biomolecular Structure and Dynamics, 36(12), 3218–3230. doi:10.1080/07391102.2017.1384401
  • Xiang, T., Jia, Y., Sherris, D., Li, S., Wang, H., Lu, D., & Yang, Q. (2011). Targeting the Akt/mTOR pathway in Brca1-deficient cancers. Oncogene, 30(21), 2443–2450. doi:10.1038/onc.2010.603
  • Yang, H., Rudge, D. G., Koos, J. D., Vaidialingam, B., Yang, H. J., & Pavletich, N. P. (2013). mTOR kinase structure, mechanism and regulation. Nature, 497(7448), 217–223. doi:10.1038/nature12122

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.