References
- A. Anighoro, J. Bajorath, and G. Rastelli, Polypharmacology: Challenges and opportunities in drug discovery, J. Med. Chem. 57 (2014), pp. 7874–7887. doi:https://doi.org/10.1021/jm5006463.
- W.C. Hahn, J.S. Bader, T.P. Braun, A. Califano, P.A. Clemons, B.J. Druker, A.J. Ewald, H. Fu, S. Jagu, C.J. Kemp, W. Kim, C.J. Kuo, M. McManus, G.B. Mills, X. Mo, N. Sahni, S.L. Schreiber, J.A. Talamas, P. Tamayo, J.W. Tyner, B.K. Wagner, W.A. Weiss, D.S. Gerhard, V. Dancik, S. Gill, B. Hua, T. Sharifnia, V. Viswanathan, Y. Zou, F. Dela Cruz, A. Kung, B. Stockwell, J. Boehm, J. Dempster, R. Manguso, F. Vazquez, L.A.D. Cooper, Y. Du, A. Ivanov, S. Lonial, C.S. Moreno, Q. Niu, T. Owonikoko, S. Ramalingam, M. Reyna, W. Zhou, C. Grandori, I. Shmulevich, E. Swisher, J. Cai, I.S. Chan, M. Dunworth, Y. Ge, D. Georgess, E.M. Grasset, E. Henriet, H. Knútsdóttir, M.G. Lerner, V. Padmanaban, M.C. Perrone, Y. Suhail, Y. Tsehay, M. Warrier, Q. Morrow, T. Nechiporuk, N. Long, J. Saultz, A. Kaempf, J. Minnier, C.E. Tognon, S.E. Kurtz, A. Agarwal, J. Brown, K. Watanabe-Smith, T.Q. Vu, T. Jacob, Y. Yan, B. Robinson, E.F. Lind, Y. Kosaka, E. Demir, J. Estabrook, M. Grzadkowski, O. Nikolova, K. Chen, B. Deneen, H. Liang, M.C. Bassik, A. Bhattacharya, K. Brennan, C. Curtis, O. Gevaert, H.P. Ji, K.A.J. Karlsson, K. Karagyozova, Y.-H. Lo, K. Liu, M. Nakano, A. Sathe, A.R. Smith, K. Spees, W.H. Wong, K. Yuki, M. Hangauer, D.S. Kaufman, A. Balmain, S.R. Bollam, W.-C. Chen, Q. Fan, K. Kersten, M. Krummel, Y.R. Li, M. Menard, N. Nasholm, C. Schmidt, N.K. Serwas, and H. Yoda, An expanded universe of cancer targets, Cell 184 (2021), pp. 1142–1155. doi:https://doi.org/10.1016/j.cell.2021.02.020.
- O.A. Kharenko, R.G. Patel, S.D. Brown, C. Calosing, A. White, D. Lakshminarasimhan, R.K. Suto, B.C. Duffy, D.B. Kitchen, K.G. McLure, H.C. Hansen, E.H. van der Horst, and P.R. Young, Design and characterization of novel covalent bromodomain and extra-terminal domain (BET) inhibitors targeting a methionine, J. Med. Chem. 61 (2018), pp. 8202–8211. doi:https://doi.org/10.1021/acs.jmedchem.8b00666.
- A. Dey, F. Chitsaz, A. Abbasi, T. Misteli, and K. Ozato, The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis, Proc. Natl. Acad. Sci. 100 (2003), pp. 8758. doi:https://doi.org/10.1073/pnas.1433065100.
- S.-Y. Wu, and C.-M. Chiang, The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation, J. Biol. Chem. 282 (2007), pp. 13141–13145. doi:https://doi.org/10.1074/jbc.R700001200.
- -M.-M. Coudé, T. Braun, J. Berrou, M. Dupont, S. Bertrand, A. Masse, E. Raffoux, R. Itzykson, M. Delord, M.E. Riveiro, P. Herait, A. Baruchel, H. Dombret, and C. Gardin, BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells, Oncotarget 6 (2015), pp. 17698–17712. doi:https://doi.org/10.18632/oncotarget.4131.
- P. Filippakopoulos, and S. Knapp, Targeting bromodomains: Epigenetic readers of lysine acetylation, Nat. Rev. Drug Discov. 13 (2014), pp. 337–356. doi:https://doi.org/10.1038/nrd4286.
- P. Filippakopoulos, J. Qi, S. Picaud, Y. Shen, W.B. Smith, O. Fedorov, E.M. Morse, T. Keates, T.T. Hickman, I. Felletar, M. Philpott, S. Munro, M.R. McKeown, Y. Wang, A.L. Christie, N. West, M.J. Cameron, B. Schwartz, T.D. Heightman, N. La Thangue, C.A. French, O. Wiest, A.L. Kung, S. Knapp, and J.E. Bradner, Selective inhibition of BET bromodomains, Nature 468 (2010), pp. 1067–1073. doi:https://doi.org/10.1038/nature09504.
- O. Mirguet, R. Gosmini, J. Toum, C.A. Clément, M. Barnathan, J.-M. Brusq, J.E. Mordaunt, R.M. Grimes, M. Crowe, O. Pineau, M. Ajakane, A. Daugan, P. Jeffrey, L. Cutler, A.C. Haynes, N.N. Smithers, C.-W. Chung, P. Bamborough, I.J. Uings, A. Lewis, J. Witherington, N. Parr, R.K. Prinjha, and E. Nicodème, Discovery of epigenetic regulator I-BET762: Lead optimization to afford a clinical candidate inhibitor of the BET bromodomains, J. Med. Chem. 56 (2013), pp. 7501–7515. doi:https://doi.org/10.1021/jm401088k.
- S.W.J. Ember, J.-Y. Zhu, S.H. Olesen, M.P. Martin, A. Becker, N. Berndt, G.I. Georg, and E. Schönbrunn, Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors, ACS Chem. Biol. 9 (2014), pp. 1160–1171. doi:https://doi.org/10.1021/cb500072z.
- S. Picaud, C. Wells, I. Felletar, D. Brotherton, S. Martin, P. Savitsky, B. Diez-Dacal, M. Philpott, C. Bountra, H. Lingard, O. Fedorov, S. Müller, P.E. Brennan, S. Knapp, and P. Filippakopoulos, RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain, Proc. Natl. Acad. Sci. 110 (2013), pp. 19754–19759. doi:https://doi.org/10.1073/pnas.1310658110.
- J. Hu, Y. Wang, Y. Li, L. Xu, D. Cao, S. Song, M.S. Damaneh, X. Wang, T. Meng, Y.-L. Chen, J. Shen, Z. Miao, and B. Xiong, Discovery of a series of dihydroquinoxalin-2(1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor, Eur. J. Med. Chem. 137 (2017), pp. 176–195. doi:https://doi.org/10.1016/j.ejmech.2017.05.049.
- Z. Liu, B. Tian, H. Chen, P. Wang, A.R. Brasier, and J. Zhou, Discovery of potent and selective BRD4 inhibitors capable of blocking TLR3-induced acute airway inflammation, Eur. J. Med. Chem. 151 (2018), pp. 450–461. doi:https://doi.org/10.1016/j.ejmech.2018.04.006.
- N.-Y. Wang, Y. Xu, K.-J. Xiao, W.-Q. Zuo, Y.-X. Zhu, R. Hu, W.-L. Wang, Y.-J. Shi, L.-T. Yu, and Z.-H. Liu, Design, synthesis, and biological evaluation of 4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine derivatives as novel dual-PLK1/BRD4 inhibitors, Eur. J. Med. Chem. 191 (2020), pp. 112152. doi:https://doi.org/10.1016/j.ejmech.2020.112152.
- P. Ciceri, S. Müller, A. O’Mahony, O. Fedorov, P. Filippakopoulos, J.P. Hunt, E.A. Lasater, G. Pallares, S. Picaud, C. Wells, S. Martin, L.M. Wodicka, N.P. Shah, D.K. Treiber, and S. Knapp, Dual kinase-bromodomain inhibitors for rationally designed polypharmacology, Nat. Chem. Biol. 10 (2014), pp. 305–312. doi:https://doi.org/10.1038/nchembio.1471.
- K. Lv, W. Chen, D. Chen, J. Mou, H. Zhang, T. Fan, Y. Li, D. Cao, X. Wang, L. Chen, J. Shen, D. Pei, and B. Xiong, Rational design and evaluation of 6-(Pyrimidin-2-ylamino)-3,4-dihydroquinoxalin-2(1H)-ones as polypharmacological inhibitors of BET and kinases, J. Med. Chem. 63 (2020), pp. 9787–9802. doi:https://doi.org/10.1021/acs.jmedchem.0c00962.
- R. Tumdam, A. Kumar, N. Subbarao, and B.S. Balaji, In silico study directed towards identification of novel high-affinity inhibitors targeting an oncogenic protein: BRD4-BD1, SAR QSAR Environ. Res. 29 (2018), pp. 975–996. doi:https://doi.org/10.1080/1062936X.2018.1537301.
- S.L. Wu, L.F. Wang, H.B. Sun, W. Wang, and Y.X. Yu, Probing molecular mechanism of inhibitor bindings to bromodomain-containing protein 4 based on molecular dynamics simulations and principal component analysis, SAR QSAR Environ. Res. 31 (2020), pp. 547–570. doi:https://doi.org/10.1080/1062936X.2020.1777584.
- L.F. Wang, Y. Wang, Z.Y. Yang, J. Zhao, H.B. Sun, and S.L. Wu, Revealing binding selectivity of inhibitors toward bromodomain-containing proteins 2 and 4 using multiple short molecular dynamics simulations and free energy analyses, SAR QSAR Environ. Res. 31 (2020), pp. 373–398. doi:https://doi.org/10.1080/1062936X.2020.1748107.
- J.-B. Tong, D. Luo, Y. Feng, S. Bian, X. Zhang, and T.-H. Wang, Structural modification of 4, 5-dihydro-[1, 2, 4] triazolo [4, 3-f] pteridine derivatives as BRD4 inhibitors using 2D/3D-QSAR and molecular docking analysis, Mol. Diversity 25 (2021), pp. 1855–1872. doi:https://doi.org/10.1007/s11030-020-10172-5.
- J.-B. Tong, D. Luo, S. Bian, and X. Zhang, Structural investigation of tetrahydropteridin analogues as selective PLK1 inhibitors for treating cancer through combined QSAR techniques, molecular docking, and molecular dynamics simulations, J. Mol. Liq. 335 (2021), pp. 116235. doi:https://doi.org/10.1016/j.molliq.2021.116235.
- J. Tong, T. Wang, and Y. Feng, Drug design and molecular docking simulations of Polo-like kinase 1 inhibitors based on QSAR study, New J. Chem. 44 (2020), pp. 21134–21145. doi:https://doi.org/10.1039/D0NJ04367B.
- A.R. de Lera and A. Ganesan, Epigenetic polypharmacology: From combination therapy to multitargeted drugs, Clin. Epigenet. 8 (2016), pp. 105. doi:https://doi.org/10.1186/s13148-016-0271-9.
- Y.-L. Wang, F. Wang, -X.-X. Shi, C.-Y. Jia, F.-X. Wu, G.-F. Hao, and G.-F. Yang, Cloud 3D-QSAR: A web tool for the development of quantitative structure–activity relationship models in drug discovery, Briefings Bioinf. 22 (2020). doi:https://doi.org/10.1093/bib/bbaa276.
- N. Cabrera, J.R. Mora, E. Márquez, V. Flores-Morales, L. Calle, and E. Cortés, QSAR and molecular docking modelling of anti-leishmanial activities of organic selenium and tellurium compounds, SAR QSAR Environ. Res. 32 (2021), pp. 29–50. doi:https://doi.org/10.1080/1062936X.2020.1848914.
- R.D. Cramer and B. Wendt, Template CoMFA: The 3D-QSAR Grail?, J. Chem. Inf. Model. 54 (2014), pp. 660–671. doi:https://doi.org/10.1021/ci400696v.
- J.-B. Tong, D. Luo, H.-Y. Xu, S. Bian, X. Zhang, X.-C. Xiao, and J. Wang, A computational approach for designing novel SARS-CoV-2 Mpro inhibitors: Combined QSAR, molecular docking, and molecular dynamics simulation techniques, New J. Chem. 45 (2021), pp. 11512–11529. doi:https://doi.org/10.1039/D1NJ02127C.
- J. Verma, V.M. Khedkar, and E.C. Coutinho, 3D-QSAR in drug design - A review, Curr. Top. Med. Chem. 10 (2010), pp. 95–115. doi:https://doi.org/10.2174/156802610790232260.
- S.L. Cunningham, A.R. Cunningham, and B.W. Day, CoMFA, HQSAR and molecular docking studies of butitaxel analogues with β-tubulin, J. Mol. Model. 11 (2005), pp. 48–54. doi:https://doi.org/10.1007/s00894-004-0220-y.
- C.-J. Liu, Y.-P. Liu, S.-L. Yu, X.-J. Dai, T. Zhang, and J.-C. Tao, Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents, Bioorg. Med. Chem. Lett. 26 (2016), pp. 5455–5461. doi:https://doi.org/10.1016/j.bmcl.2016.10.028.
- S. Wold, M. Sjöström, and L. Eriksson, PLS-regression: A basic tool of chemometrics, Chemom. Intell. Lab. 58 (2001), pp. 109–130. doi:https://doi.org/10.1016/S0169-7439(01)00155-1.
- J. Tu, L.T. Song, H.L. Zhai, J. Wang, and X.Y. Zhang, Selective mechanisms and molecular design of 2,4 Diarylaminopyrimidines as ALK inhibitors, Int. J. Biol. Macromol. 118 (2018), pp. 1149–1156. doi:https://doi.org/10.1016/j.ijbiomac.2018.06.192.
- A. Golbraikh and A. Tropsha, Beware of q2!, J. Mol. Graphics Modell. 20 (2002), pp. 269–276. doi:https://doi.org/10.1016/S1093-3263(01)00123-1.
- P. de Cerqueira Lima, A. Golbraikh, S. Oloff, Y. Xiao, and A. Tropsha, Combinatorial QSAR modeling of P-Glycoprotein Substrates, J. Chem. Inf. Model. 46 (2006), pp. 1245–1254. doi:https://doi.org/10.1021/ci0504317.
- X.X. Peng, K.R. Feng, and Y.J. Ren, Molecular modeling studies of quinazolinone derivatives as novel PI3Kδ selective inhibitors, RSC Adv. 7 (2017), pp. 56344–56358. doi:https://doi.org/10.1039/C7RA10870B.
- G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, and A.J. Olson, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J. Comput. Chem. 30 (2009), pp. 2785–2791. doi:https://doi.org/10.1002/jcc.21256.
- O. Trott and A.J. Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem. 31 (2010), pp. 455–461.
- D. Van Der Spoel, E. Lindahl, B. Hess, G. Groenhof, A.E. Mark, and H.J.C. Berendsen, GROMACS: Fast, flexible, and free, J. Comput. Chem. 26 (2005), pp. 1701–1718. doi:https://doi.org/10.1002/jcc.20291.
- J. Huang and A.D. MacKerell Jr, CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data, J. Comput. Chem. 34 (2013), pp. 2135–2145. doi:https://doi.org/10.1002/jcc.23354.
- K. Vanommeslaeghe and A.D. MacKerell, Automation of the CHARMM General Force Field (CGenFF) I: Bond perception and atom typing, J. Chem. Inf. Model. 52 (2012), pp. 3144–3154. doi:https://doi.org/10.1021/ci300363c.
- D.M.F. Van Aalten, B.L. De Groot, J.B.C. Findlay, H.J.C. Berendsen, and A. Amadei, A comparison of techniques for calculating protein essential dynamics, J. Comput. Chem. 18 (1997), pp. 169–181. doi:https://doi.org/10.1002/(SICI)1096-987X(19970130)18:2<169::AID-JCC3>3.0.CO;2-T.
- A. Grottesi, N. Bešker, A. Emerson, C. Manelfi, A.R. Beccari, F. Frigerio, E. Lindahl, C. Cerchia, and C. Talarico, Computational studies of SARS-CoV-2 3CLpro: Insights from MD simulations, Int. J. Mol. Sci. 21 (2020), pp. 5346. doi:https://doi.org/10.3390/ijms21155346.
- Z.T. Muhseen, A.R. Hameed, H.M.H. Al-Hasani, M. Tahir Ul Qamar, and G. Li, Promising terpenes as SARS-CoV-2 spike receptor-binding domain (RBD) attachment inhibitors to the human ACE2 receptor: Integrated computational approach, J. Mol. Liq. 320 (2020), pp. 114493. doi:https://doi.org/10.1016/j.molliq.2020.114493.
- T. Hou, J. Wang, Y. Li, and W. Wang, Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations, J. Chem. Inf. Model. 51 (2011), pp. 69–82. doi:https://doi.org/10.1021/ci100275a.
- G. Xiong, Z. Wu, J. Yi, L. Fu, Z. Yang, C. Hsieh, M. Yin, X. Zeng, C. Wu, A. Lu, X. Chen, T. Hou, and D. Cao, ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties, Nucleic Acids Res. 49 (2021), pp. W5–W14. doi:https://doi.org/10.1093/nar/gkab255.
- A. Daina, O. Michielin, and V. Zoete, SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep. 7 (2017), pp. 42717. doi:https://doi.org/10.1038/srep42717.
- M. Tonelli, S. Espinoza, R.R. Gainetdinov, and E. Cichero, Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies, Eur. J. Med. Chem. 127 (2017), pp. 781–792. doi:https://doi.org/10.1016/j.ejmech.2016.10.058.
- C. Brullo, R. Ricciarelli, J. Prickaerts, O. Arancio, M. Massa, C. Rotolo, A. Romussi, C. Rebosio, B. Marengo, M.A. Pronzato, B.T.J. van Hagen, N.P. van Goethem, P. D’Ursi, A. Orro, L. Milanesi, S. Guariento, E. Cichero, P. Fossa, E. Fedele, and O. Bruno, New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment, Eur. J. Med. Chem. 124 (2016), pp. 82–102. doi:https://doi.org/10.1016/j.ejmech.2016.08.018.