Abstract
Objective: To obtain potent PI3Kγ inhibitors precursor from SPECS database via the method of molecular docking. Methods: Active molecules can be obtained by screening the database. The protein targets were obtained by the SC-PDB database and the Pyrx software under Aotodock-vina was used to screening. Before screening, the reliability of the model was assessed by calculating the root mean square deviation RMSD and the enrichment factor. Cell experiments were carried out by the selected molecules. Results: 28 molecules were obtained by screening. Through the test of molecular cell level, an inhibitor molecule was obtained. The Smile format was c12n (ncc1C (=O) N/N=C (/c1cc (NC) (=O) C). Conclusion: The Smile is a new effective PI3K γ inhibitor precursor molecule. This study provides reference for the development of PI3Kγ inhibitors.
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References
Wu, C., Zhao, J., Zhou, Z., et al.: Selective PI3K inhibitors research progress. Chin. Pharmacol. 4, 305–310 (2014)
Krasilnikov, M.A.: Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. Biochemistry (Moscow) 65(1), 59–67 (2000)
Vogt, P.K., Gymnopoulos, M., Hart, J.R.: PI3K-kinase and cancer: changing accents. Curr. Opin. Genet. Dev. 19(1), 1–17 (2009)
Denley, A., Gymnopoulos, M., Kang, S., et al.: Requirement of phosphatidylinositol(3,4,5)trisphosphate (PIP3) in PI3K-induced oncogenic transformation. Mol. Cancer Res. MCR 7(7), 1132 (2009)
Uzumcu, M., Westfall, S.D., Dirks, K.A., et al.: Embryonic testis cord formation and mesonephric cell migration requires the phosphotidylinositol 3-kinase signaling pathway. Biol. Reprod. 67(6), 1927–1935 (2002)
Li, T., Wang, G.: Computer-aided targeting of the PI3K/Akt/mTOR pathway: toxicity reduction and therapeutic opportunities. Int. J. Mol. Sci. 15(10), 18856–18891 (2014)
Rodon, J., Dienstmann, R., Serra, V., et al.: Development of PI3K inhibitors: lessons learned from early clinical trials. Nat. Rev. Clin. Oncol. 10(3), 143–153 (2013)
Kaneda, M.M., Messer, K.S., Ralainirina, N.: Corrigendum PI3Kγ is a molecular switch that controls immune suppression. Nature 539(7629), 437–442 (2016)
Chiang, M.R., Wei, C.C., Muo, C.S., et al.: Association of primary immune thrombocytopenia and common allergic diseases among children. Pediatr. Res. 77(4), 597–601 (2015)
Nagai, S., Kurebayashi, Y., Koyasu, S.: Role of PI3K/Akt and mTOR complexes in Th17 cell differentiation. Ann. N. Y. Acad. Sci. 1280(1), 30–34 (2013)
Venable, J.D., Ameriks, M.K., Blevitt, J.M., et al.: Phosphoinositide 3-kinase gamma (PI3Kgamma) inhibitors for the treatment of inflammation and autoimmune disease. Recent Pat. Inflammation Allergy Drug Discovery 4(1), 1–15 (2010)
Chen, W.W., Gao, R.L., Liu, L.S., et al.: China cardiovascular diseases report 2015: a summary. J. Geriatr. Cardiol. 14(1), 1–10 (2017)
Stumvoll, M.: Thiazolidinediones – some recent developments. Expert Opin. Investig. Drugs 12(7), 1179–1187 (2003)
Yuan, T.L., Cantley, L.C.: PI3K pathway alterations in cancer: variations on a theme. Oncogene 27(41), 5497–5510 (2008)
Boucher, E., Forner, A., Reig, M., et al.: New drugs for the treatment of hepatocellular carcinoma. Liver Int. Off. J. Int. Assoc. Study Liver 29(s1), 148–158 (2010)
Frédérick, R., Mawson, C., Kendall, J.D., et al.: Phosphoinositide-3-kinase (PI3K) inhibitors: identification of new scaffolds using virtual screening. Bioorg. Med. Chem. Lett. 19(20), 5842–5847 (2009)
Giordanetto, F., Kull, B., Dellsén, A.: Discovery of novel class 1 phosphatidylinositide 3-kinases (PI3K) fragment inhibitors through structure-based virtual screening. Bioorg. Med. Chem. Lett. 21(2), 829–835 (2011)
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The authors thank SPECS company for providing the compounds for testing. Competing Interests. We have no competing interests.
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Luo, B., Chen, S., Guo, Y., Ren, Y. (2020). Computer Aided Screening of PI3K Inhibitor Molecules from Database. In: Hung, J., Yen, N., Chang, JW. (eds) Frontier Computing. FC 2019. Lecture Notes in Electrical Engineering, vol 551. Springer, Singapore. https://doi.org/10.1007/978-981-15-3250-4_95
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DOI: https://doi.org/10.1007/978-981-15-3250-4_95
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