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Original Articles

Identification of inhibitors targeting HIF-2α/c-Myc by molecular docking and MM-GBSA technology

ORCID Icon, , , , &
Pages 511-519 | Received 24 Aug 2020, Accepted 14 Sep 2020, Published online: 27 Sep 2020

References

  • W K. Kidney Cancer. Principles and practice. Vol. 3. Switzerland: Springer International Publishing; 2015. p. 31–57.
  • Semenza GL. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci Stke. 2007;2007(407):cm8.
  • Fallah J, Rini BI. HIF inhibitors: status of current clinical development. Curr Oncol Rep. 2019;21(1):6.
  • Krieg M, Haas R, Brauch H, et al. Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene. 2000;19(48):5435–5443.
  • Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9(6):653–660.
  • Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003;9(6):677–684.
  • Kelly BD, Hackett SF, Hirota K, et al. Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res. 2003;93(11):1074–1081.
  • Koh MY, Lemos R, Liu X, et al. The hypoxia-associated factor switches cells from HIF-1α- to HIF-2α-dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion. Cancer Res. 2011;71(11):4015–4027.
  • Raval RR, Lau KW, Tran MGB, et al. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol Cell Biol. 2005;25(13):5675–5686.
  • Koehler AN. A complex task? Direct modulation of transcription factors with small molecules. Curr Opin Chem Biol. 2010;14(3):331–340.
  • Cho H, Du X, Rizzi JP, et al. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature. 2016;539(7627):107–111.
  • Wallace EM, Rizzi JP, Han G, et al. A small-molecule antagonist of HIF2α is efficacious in preclinical models of renal cell carcinoma. Cancer Res. 2016;76(18):5491–5500.
  • Eli Wallace PD. PT2385: HIF-2α Antagonist for the Treatment of VHL Mutant ccRCC. 12th International VHL Medical Symposium April 82016.
  • Xu R, Wang K, Rizzi JP, et al. 3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977), a hypoxia-inducible factor 2α (HIF-2α) inhibitor for the treatment of clear cell renal cell carcinoma. J Med Chem. 2019;62(15):6876–6893.
  • Scheuermann TH, Tomchick DR, Machius M, et al. Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor. Proc Natl Acad Sci USA. 2009;106(2):450–455.
  • Gordan JD, Lal P, Dondeti VR, et al. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell. 2008;14(6):435–446.
  • Koshiji M, Kageyama Y, Pete EA, et al. HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. Embo J. 2004;23(9):1949–1956.
  • Gordan JD, Bertout JA, Hu C-J, et al. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell. 2007;11(4):335–347.
  • Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol. 2005;6(8):635–645.
  • Nilsson JA, Cleveland JL. Myc pathways provoking cell suicide and cancer. Oncogene. 2003;22(56):9007–9021.
  • Nair SK, Burley SK. X-Ray structures of Myc-max and mad-max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Cell. 2003;112(2):193–205.
  • Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res. 2000;28(1):235–242.
  • 2017-4 SR. Maestro. 2017-4. New York (NY): Schrödinger, LLC; 2017.
  • Sastry GM, Adzhigirey M, Day T, et al. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des. 2013;27(3):221–234.
  • 2017-4 SR. Schrödinger suite 2017-4 protein preparation wizard. 2017-4. New York (NY): Schrödinger, LLC; 2017. Impact, Schrödinger. New York (NY): LLC; 2016. Prime, Schrödinger. New York (NY): LLC, 2017. Epik, Schrödinger. New York (NY): LLC; 2016.
  • Harder E, Damm W, Maple J, et al. OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. J Chem Theory Comput. 2016;12(1):281–296.
  • Irwin JJ, Shoichet BK. ZINC-a free database of commercially available compounds for virtual screening. J Chem Inf Model. 2005;45(1):177–182.
  • Irwin JJ, Sterling T, Mysinger MM, et al. ZINC: a free tool to discover chemistry for biology. J Chem Inf Model. 2012;52(7):1757–1768.
  • Molecular Operating Environment (MOE). 2013-8. 1010 Sherbooke St. West., Suite #910, Montreal (QC): Chemical Computing Group ULC; 2018.
  • 2017-4 SR. SiteMap. 2017-4. New York (NY): Schrödinger, LLC; 2017.
  • Halgren TA. Identifying and characterizing binding sites and assessing druggability. J Chem Inf Model. 2009;49(2):377–389.
  • Halgren T. New method for fast and accurate binding-site identification and analysis. Chem Biol Drug Des. 2007;69(2):146–148.
  • 2017-4 SR. Glide. 2017-4. New York (NY): Schrödinger, LLC; 2017.
  • Halgren TA, Murphy RB, Friesner RA, et al. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem. 2004;47(7):1750–1759.
  • Friesner RA, Banks JL, Murphy RB, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47(7):1739–1749.
  • Friesner RA, Murphy RB, Repasky MP, et al. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem. 2006;49(21):6177–6196.
  • 2017-4 SR. Phase. 2017-4. New York (NY): Schrödinger, LLC; 2017.
  • Sun H, Li Y, Shen M, et al. Assessing the performance of MM/PBSA and MM/GBSA methods. 5. Improved docking performance using high solute dielectric constant MM/GBSA and MM/PBSA rescoring [https://doi.org/10.1039/C4CP03179B. Phys Chem Chem Phys. 2014;16(40):22035–22045.
  • Kollman PA, Massova I, Reyes C, et al. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res. 2000;33(12):889–897.
  • Abraham MJ, Murtola T, Schulz R, et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1–2:19–25.
  • Oostenbrink C, Villa A, Mark AE, et al. A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem. 2004;25(13):1656–1676.
  • Schuttelkopf AW, van Aalten DMF. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr. 2004;60(Pt 8):1355–1363.
  • Ferré-D’Amaré AR, Prendergast GC, Ziff EB, et al. Recognition by max of its cognate DNA through a dimeric b/HLH/Z domain. Nature. 1993;363(6424):38–45.
  • Jung LA, Gebhardt A, Koelmel W, et al. OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors. Oncogene. 2017;36(14):1911–1924.
  • Carabet LA, Lallous N, Leblanc E, et al. Computer-aided drug discovery of Myc-Max inhibitors as potential therapeutics for prostate cancer. Eur J Med Chem. 2018;160:108–119.
  • Erbel PJA, Card PB, Karakuzu O, et al. Structural basis for PAS domain heterodimerization in the basic helix-loop-helix-PAS transcription factor hypoxia-inducible factor. Proc Natl Acad Sci USA. 2003;100(26):15504–15509.
  • Sun D-R, Wang Z-J, Zheng Q-C, et al. Exploring the inhibition mechanism on HIF-2 by inhibitor PT2399 and 0X3 using molecular dynamics simulations. J Mol Recognit. 2018;31(10):e2730.

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