132
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Identification of new small molecule allosteric SHP2 inhibitor through pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation studies, synthesis and in vitro evaluation

ORCID Icon, ORCID Icon & ORCID Icon
Received 02 Aug 2023, Accepted 15 Nov 2023, Published online: 14 Dec 2023

References

  • Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., & Lindahl, E. (2015). GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1–2, 19–25. https://doi.org/10.1016/j.softx.2015.06.001
  • Asmamaw, M. D., Shi, X.-J., Zhang, L.-R., & Liu, H.-M. (2022). A comprehensive review of SHP2 and its role in cancer. Cellular Oncology (Dordrecht), 45(5), 729–753. https://doi.org/10.1007/s13402-022-00698-1
  • Baell, J. B., & Holloway, G. A. (2010). New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. Journal of Medicinal Chemistry, 53(7), 2719–2740. https://doi.org/10.1021/jm901137j
  • Berman, H., Henrick, K., & Nakamura, H. (2003). Announcing the worldwide Protein Data Bank. Nature Structural Biology, 10(12), 980–980. https://doi.org/10.1038/nsb1203-980
  • Biovia, D. S. (2021). Discovery studio visualizer. Dassault Systemes.
  • Bramucci, E., et al. (2012). PyMod: Sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL. Italian Society of Bioinformatics (BITS), 13(4), 1–6. https://doi.org/10.1186/1471-2105-13-s4-s2
  • CCG, Inc. (2016). Molecular operating environment (MOE), Chemical Computing Group Inc 1010 Sherbooke St. West, Suite# 910, Montreal QC, Canada, 2016.
  • Chan, G., Kalaitzidis, D., & Neel, B. G. (2008). The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer Metastasis Reviews, 27(2), 179–192. https://doi.org/10.1007/s10555-008-9126-y
  • Chen, Y.-N P., LaMarche, M. J., Chan, H. M., Fekkes, P., Garcia-Fortanet, J., Acker, M. G., Antonakos, B., Chen, C. H.-T., Chen, Z., Cooke, V. G., Dobson, J. R., Deng, Z., Fei, F., Firestone, B., Fodor, M., Fridrich, C., Gao, H., Grunenfelder, D., Hao, H.-X., … Fortin, P. D. (2016). Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature, 535(7610), 148–152. https://doi.org/10.1038/nature18621
  • Cheng, F., Li, W., Zhou, Y., Shen, J., Wu, Z., Liu, G., Lee, P. W., & Tang, Y. (2012). admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. Journal of Chemical Information and Modeling, 52(11), 3099–3105. https://doi.org/10.1021/ci300367a
  • Eisenhaber, F., Lijnzaad, P., Argos, P., Sander, C., & Scharf, M. (1995). The double cubic lattice method: Efficient approaches to numerical integration of surface area and volume and to dot surface contouring of molecular assemblies. Journal of Computational Chemistry, 16(3), 273–284. https://doi.org/10.1002/jcc.540160303
  • Galluzzi, L., Kepp, O., Vander Heiden, M. G., & Kroemer, G. (2013). Metabolic targets for cancer therapy. Nature Reviews Drug Discovery, 12(11), 829–846. https://doi.org/10.1038/nrd4145
  • Garcia Fortanet, J., Chen, C. H.-T., Chen, Y.-N P., Chen, Z., Deng, Z., Firestone, B., Fekkes, P., Fodor, M., Fortin, P. D., Fridrich, C., Grunenfelder, D., Ho, S., Kang, Z. B., Karki, R., Kato, M., Keen, N., LaBonte, L. R., Larrow, J., Lenoir, F., … LaMarche, M. J. (2016). Allosteric inhibition of SHP2: Identification of a potent, selective, and orally efficacious phosphatase inhibitor. Journal of Medicinal Chemistry, 59(17), 7773–7782. https://doi.org/10.1021/acs.jmedchem.6b00680
  • Gee, K. R., Sun, W. C., Bhalgat, M. K., Upson, R. H., Klaubert, D. H., Latham, K. A., & Haugland, R. P. (1999). Fluorogenic substrates based on fluorinated umbelliferones for continuous assays of phosphatases and beta-galactosidases. Analytical Biochemistry, 273(1), 41–48. https://doi.org/10.1006/abio.1999.4202
  • Ghemrawi, R., Khair, M., Hasan, S., Aldulaymi, R., AlNeyadi, S. S., Atatreh, N., & Ghattas, M. A. (2022). The discovery of potent SHP2 inhibitors with anti-proliferative activity in breast cancer cell lines. International Journal of Molecular Sciences, 23(8), 4468. https://doi.org/10.3390/ijms23084468
  • Giordano, D., Biancaniello, C., Argenio, M. A., & Facchiano, A. (2022). Drug design by pharmacophore and virtual screening approach. Pharmaceuticals (Basel, Switzerland), 15(5), 646. https://doi.org/10.3390/ph15050646
  • Grygorenko, O. O. (2021). The science and business of organic chemistry and beyond. European Journal of Organic Chemistry, 2021(47), 6474–6477. https://doi.org/10.1002/ejoc.202101210
  • Jin, W.-Y., Ma, Y., Li, W.-Y., Li, H.-L., & Wang, R.-L. (2018). Scaffold-based novel SHP2 allosteric inhibitors design using Receptor-Ligand pharmacophore model, virtual screening and molecular dynamics. Computational Biology and Chemistry, 73, 179–188. https://doi.org/10.1016/j.compbiolchem.2018.02.004
  • Kawata, M., & Nagashima, U. (2001). Particle mesh Ewald method for three-dimensional systems with two-dimensional periodicity. Chemical Physics Letters, 340(1-2), 165–172. https://doi.org/10.1016/S0009-2614(01)00393-1
  • Kong, J., & Long, Y.-Q. (2022). Recent advances in the discovery of protein tyrosine phosphatase SHP2 inhibitors. RSC Medicinal Chemistry, 13(3), 246–257. https://doi.org/10.1039/D1MD00386K
  • Kumar, S., & Ayyannan, S. R. (2023). Identification of new small molecule monoamine oxidase-B inhibitors through pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation studies. Journal of Biomolecular Structure & Dynamics, 41(14), 6789–6810. https://doi.org/10.1080/07391102.2022.2112082
  • Kumar, S., Jaiswal, S., Gupta, S. K., & Ayyannan, S. R. (2023). Benzimidazole-derived carbohydrazones as dual monoamine oxidases and acetylcholinesterase inhibitors: Design, synthesis, and evaluation. Journal of Biomolecular Structure & Dynamics, 1–20. https://doi.org/10.1080/07391102.2023.2224887
  • Laskowski, R. A., Rullmannn, J. A., MacArthur, M. W., Kaptein, R., & Thornton, J. M. (1996). AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR. Journal of Biomolecular NMR, 8(4), 477–486. https://doi.org/10.1007/bf00228148
  • Lipinski, C. (2004). Lead-and drug-like compounds: The rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007
  • Liu, W.-S., Jin, W.-Y., Zhou, L., Lu, X.-H., Li, W.-Y., Ma, Y., & Wang, R.-L. (2019). Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation. Journal of Computer-Aided Molecular Design, 33(8), 759–774. https://doi.org/10.1007/s10822-019-00213-z
  • Malde, A. K., Zuo, L., Breeze, M., Stroet, M., Poger, D., Nair, P. C., Oostenbrink, C., & Mark, A. E. (2011). An automated force field topology builder (ATB) and repository: Version 1.0. Journal of Chemical Theory and Computation, 7(12), 4026–4037. https://doi.org/10.1021/ct200196m
  • Mitra, R., & Ayyannan, S. R. (2021). Small-molecule inhibitors of Shp2 phosphatase as potential chemotherapeutic agents for glioblastoma: A minireview. ChemMedChem. 16(5), 777–787. https://doi.org/10.1002/cmdc.202000706
  • National Library of Medicine. (2023). Clinical trials: Studies found for: Shp2 | Recruiting, Not yet recruiting, active, not recruiting, completed studies. https://clinicaltrials.gov/search?term=shp2
  • Neel, B. G., Gu, H., & Pao, L. (2003). The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends in Biochemical Sciences, 28(6), 284–293. https://doi.org/10.1016/S0968-0004(03)00091-4
  • Nunes-Xavier, C. E., Mingo, J., López, J. I., & Pulido, R. (2019). The role of protein tyrosine phosphatases in prostate cancer biology. Biochimica et Biophysica Acta. Molecular Cell Research, 1866(1), 102–113. https://doi.org/10.1016/j.bbamcr.2018.06.016
  • Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera—a visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25(13), 1605–1612. https://doi.org/10.1002/jcc.20084
  • Qu, C. K. (2000). The SHP-2 tyrosine phosphatase: Signaling mechanisms and biological functions. Cell Research, 10(4), 279–288. https://doi.org/10.1038/sj.cr.7290055
  • Richards, C. E., Elamin, Y. Y., Carr, A., Gately, K., Rafee, S., Cremona, M., Hanrahan, E., Smyth, R., Ryan, D., Morgan, R. K., Kennedy, S., Hudson, L., Fay, J., O'Byrne, K., Hennessy, B. T., & Toomey, S. (2023). Protein tyrosine phosphatase non-receptor 11 (PTPN11/Shp2) as a driver oncogene and a novel therapeutic target in non-small cell lung cancer (NSCLC). International Journal of Molecular Sciences, 24(13), 10545. https://doi.org/10.3390/ijms241310545
  • Saez-Ayala, M., Hoffer, L., Abel, S., Ben Yaala, K., Sicard, B., Andrieu, G. P., Latiri, M., Davison, E. K., Ciufolini, M. A., Brémond, P., Rebuffet, E., Roche, P., Derviaux, C., Voisset, E., Montersino, C., Castellano, R., Collette, Y., Asnafi, V., Betzi, S., … Morelli, X. (2023). From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia. Nature Communications, 14(1), 3079. https://doi.org/10.1038/s41467-023-38668-2
  • Savitzky, A., & Golay, M. J. E. (1964). Smoothing and differentiation of data by simplified least squares procedures. Analytical Chemistry, 36(8), 1627–1639. https://doi.org/10.1021/ac60214a047
  • Sever, R., & Brugge, J. S. (2015). Signal transduction in cancer. Cold Spring Harbor Perspectives in Medicine, 5(4), a006098–a006098. https://doi.org/10.1101/cshperspect.a006098
  • Song, Y., Zhao, M., Zhang, H., & Yu, B. (2022). Double-edged roles of protein tyrosine phosphatase SHP2 in cancer and its inhibitors in clinical trials. Pharmacology & Therapeutics, 230, 107966. https://doi.org/10.1016/j.pharmthera.2021.107966
  • Sunseri, J., & Koes, D. R. (2016). Pharmit: Interactive exploration of chemical space. Nucleic Acids Research, 44(W1), W442–W448. https://doi.org/10.1093/nar/gkw287
  • Takeuchi, T., Nomura, Y., Tamita, T., Nishikawa, R., Kakinuma, H., Kojima, N., Hitaka, K., Tamura, Y., Kamitani, M., Mima, M., Nozoe, A., & Hayashi, M. (2023). Discovery of TP0597850: A selective, chemically stable, and slow tight-binding matrix metalloproteinase-2 inhibitor with a phenylbenzamide–pentapeptide hybrid scaffold. Journal of Medicinal Chemistry, 66(1), 822–836. https://doi.org/10.1021/acs.jmedchem.2c01698
  • Thomas, D., Karle, C. A., & Kiehn, J. (2006). The cardiac hERG/IKr potassium channel as pharmacological target: Structure, function, regulation, and clinical applications. Current Pharmaceutical Design, 12(18), 2271–2283. https://doi.org/10.2174/138161206777585102
  • Tripathi, R. K. P., & Ayyannan, S. R. (2021). Emerging chemical scaffolds with potential SHP2 phosphatase inhibitory capabilities – A comprehensive review. Chemical Biology & Drug Design, 97(3), 721–773. https://doi.org/10.1111/cbdd.13807
  • Tyagi, R., et al. (2022). Chapter 17 - pharmacophore modeling and its applications, in bioinformatics (D. B. Singh and R. K. Pathak, Eds., pp. 269–289). Academic Press.
  • Wang, X., Wang, R., Zhang, Z.-S., Zhang, G.-Y., Jin, Z., Shen, R., Du, D., & Tang, Y.-Z. (2022). Semisynthetic pleuromutilin antimicrobials with therapeutic potential against methicillin-resistant Staphylococcus aureus by targeting 50S ribosomal subunit. European Journal of Medicinal Chemistry, 237, 114341. https://doi.org/10.1016/j.ejmech.2022.114341
  • Wu, J., Li, W., Zheng, Z., Lu, X., Zhang, H., Ma, Y., & Wang, R. (2021). Design, synthesis, biological evaluation, common feature pharmacophore model and molecular dynamics simulation studies of ethyl 4-(phenoxymethyl)-2-phenylthiazole-5-carboxylate as Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors. Journal of Biomolecular Structure & Dynamics, 39(4), 1174–1188. https://doi.org/10.1080/07391102.2020.1726817
  • Xiang, H., Liu, R., Zhang, X., An, R., Zhou, M., Tan, C., Li, Q., Su, M., Guo, C., Zhou, L., Li, Y., & Wang, R. (2023). Discovery of small-molecule autophagy inhibitors by disrupting the protein–protein interactions involving autophagy-related 5. Journal of Medicinal Chemistry, 66(4), 2457–2476. https://doi.org/10.1021/acs.jmedchem.2c01233
  • Yu, Z.-H., Chen, L., Wu, L., Liu, S., Wang, L., & Zhang, Z.-Y. (2011). Small molecule inhibitors of SHP2 tyrosine phosphatase discovered by virtual screening. Bioorganic & Medicinal Chemistry Letters, 21(14), 4238–4242. https://doi.org/10.1016/j.bmcl.2011.05.078
  • Yuan, X., Bu, H., Zhou, J., Yang, C.-Y., & Zhang, H. (2020). Recent advances of SHP2 inhibitors in cancer therapy: Current development and clinical application. Journal of Medicinal Chemistry, 63(20), 11368–11396. https://doi.org/10.1021/acs.jmedchem.0c00249
  • Zeiger, E. (2019). The test that changed the world: The Ames test and the regulation of chemicals. Mutation Research. Genetic Toxicology and Environmental Mutagenesis, 841, 43–48. https://doi.org/10.1016/j.mrgentox.2019.05.007
  • Zhou, R. (2003). Free energy landscape of protein folding in water: Explicit vs. implicit solvent. Proteins: Structure, Function, and Bioinformatics, 53(2), 148–161. https://doi.org/10.1002/prot.10483

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.