The vinyl sulfone motif as a structural unit for novel drug design and discovery

References

• Mustafa M, Winum JY. The importance of sulfur-containing motifs in drug design and discovery. Expert Opin Drug Discov. 2022;17(5):501–512. doi: 10.1080/17460441.2022.2044783
   PubMed Web of Science ®Google Scholar
• Scott KA, Njardarson JT. Analysis of US FDA-approved drugs containing sulfur atoms. Top Curr Chem (Z). 2018;376(1):5. doi: 10.1007/s41061-018-0184-5
   PubMed Web of Science ®Google Scholar
• Meadows C, Gervay-Hague J. Vinyl sulfones: synthetic preparations and medicinal chemistry applications. Med Res Rev. 2006;26(6):793–814. doi: 10.1002/med.20074
   PubMed Web of Science ®Google Scholar
• Ahmadi R, Emami S. Recent applications of vinyl sulfone motif in drug design and discovery. Eur J Med Chem. 2022;234:114255. doi: 10.1016/j.ejmech.2022.114255
   PubMed Web of Science ®Google Scholar
• Morales-Sanfrutos J, Lopez-Jaramillo J, Ortega-Muñoz M, et al. Vinyl sulfone: a versatile function for simple bioconjugation and immobilization. Org Biomol Chem. 2010;8(3):667–675. doi: 10.1039/B920576D
   PubMed Web of Science ®Google Scholar
• Lopez-Jaramillo FJ, Hernandez-Mateo F, Santoyo-Gonzalez F. Integrative proteomics: chapter 16: vinyl sulfone: a multi-purpose function in proteomics (pages 301–326). Leung HC ed. Rijeka: InTech; 2012.
   Google Scholar
• Fang Y, Luo Z, Xu X. Recent advance in the synthesis of vinyl sulfones. RSC Adv. 2016;6:59661–59676. doi: 10.1039/C6RA10731A
   Web of Science ®Google Scholar
• Gehringer M, Laufer SA. Emerging and re-emerging warheads for targeted covalent inhibitors: applications in medicinal chemistry and chemical biology. J Med Chem. 2019;62(12):5673–5724. doi: 10.1021/acs.jmedchem.8b01153
   PubMed Web of Science ®Google Scholar
• Dahal UP, Gilbert AM, Obach RS, et al. Intrinsic reactivity profile of electrophilic moieties to guide covalent drug design: N-α-Acetyl-L-Lysine as an amine nucleophile. MedChemcomm. 2016;7(5):864–872. doi: 10.1039/C6MD00017G
   Web of Science ®Google Scholar
• Chatani S, Nair DP, Bowman CN. Relative reactivity and selectivity of vinyl sulfones and acrylates towards the thiol–Michael addition reaction and polymerization. Polym Chem. 2013;4(4):1048–1055. doi: 10.1039/C2PY20826A
   Web of Science ®Google Scholar
• Cohen P, Cross D, Jänne PA. Kinase drug discovery 20 years after imatinib: progress and future directions. Nat Rev Drug Discov. 2021;20(7):551–569. doi: 10.1038/s41573-021-00195-4
   PubMed Web of Science ®Google Scholar
• Attwood MM, Fabbro D, Sokolov AV. Trends in kinase drug discovery: Targets, indications and inhibitor design. Nat Rev Drug Discov. 2021;20(11):839–861. doi: 10.1038/s41573-021-00252-y
   PubMed Web of Science ®Google Scholar
• Khwaja S, Kumar K, Das R, et al. Microtubule associated proteins as targets for anticancer drug development. Bioorg Chem. 2021;116:105320. doi: 10.1016/j.bioorg.2021.105320
   PubMed Web of Science ®Google Scholar
• Reddy MVR, Mallireddigari MR, Cosenza SC, et al. Design, synthesis, and biological evaluation of (E)-styrylbenzylsulfones as novel anticancer agents. J Med Chem. 2008;51(1):86–100.doi: 10.1021/jm701077b
   PubMed Web of Science ®Google Scholar
• Reddy MVR, Venkatapuram P, Mallireddigari MR. Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(20,40,60-trimethoxystyrylsulfonyl)methyl] phenyl- amino}-acetate (ON 01910.Na): synthesis, structure–activity relationship, and biological activity. J Med Chem. 2011;54(18):6254–6276. doi: 10.1021/jm200570p
   PubMed Web of Science ®Google Scholar
• Athuluri-Drivakar SK, Carpio RVD, Dutta K, et al. A small molecule RAS-mimetic disrupts RAS association with effector proteins to block signaling. Cell. 2016;165(3):643–655. doi: 10.1016/j.cell.2016.03.045
   PubMed Web of Science ®Google Scholar
• Jost M, Chen Y, Gilbert LA, et al. Combined CRISPRi/a-based chemical genetic screens reveal that Rigosertib is a microtubule-destabilizing agent. Mol Cell. 2017;68(1):210–223. doi: 10.1016/j.molcel.2017.09.012
   PubMed Web of Science ®Google Scholar
• Lu T, Goh AW, Yu M, et al. Discovery of (E)‑3-((styrylsulfonyl)methyl)pyridine and (E)‑2- ((styrylsulfonyl)methyl)pyridine derivatives as anticancer agents: synthesis, structure−activity relationships, and biological activities. J Med Chem. 2014;57(6):2275–2291. doi: 10.1021/jm4019614
   PubMed Web of Science ®Google Scholar
• Reddy MVR, Mallireddigari MR, Pallela VR, et al. Design, synthesis, and biological evaluation of (E)‑N‑Aryl-2-arylethenesulfonamide analogues as potent and orally bioavailable microtubule-targeted anticancer agents. J Med Chem. 2013;56(13):5562–5586. doi: 10.1021/jm400575x
   PubMed Web of Science ®Google Scholar
• Li W, Yin Y, Yao H, et al. Discovery of novel vinyl sulfone derivatives as anti-tumor agents with microtubule polymerization inhibitory and vascular disrupting activities. Eur J Med Chem. 2018;157:1026–1080. doi: 10.1016/j.ejmech.2018.08.074
   Web of Science ®Google Scholar
• Li W, Sun H, Xu F, et al. Synthesis, molecular properties prediction and biological evaluation of indole-vinyl sulfone derivatives as novel tubulin polymerization inhibitors targeting the colchicine binding site. Bioorg Chem. 2019;85:49–59. doi: 10.1016/j.bioorg.2018.12.015
   PubMed Web of Science ®Google Scholar
• Ostrem JM, Peters U, Sos ML, et al. K-Ras (G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013;503(7477):548–551. doi: 10.1038/nature12796
   PubMed Web of Science ®Google Scholar
• Du G, Rao S, Gurbani D, et al. Structure-based design of a potent and selective covalent inhibitor for SRC kinase that targets a P-loop cysteine. J Med Chem. 2020;63(4):1624–1641. doi: 10.1021/acs.jmedchem.9b01502
   PubMed Web of Science ®Google Scholar
• Chahrour O, Abdalla A, Lam F, et al. Synthesis and biological evaluation of benzyl styrylsulfonyl derivatives as potent anticancer mitotic inhibitors. Bioorg Med Chem Lett. 2011;21(10):3066–3069. doi: 10.1016/j.bmcl.2011.03.041
   PubMed Web of Science ®Google Scholar
• Li QS, Li CY, Lu X, et al. Design, synthesis and biological evaluation of novel (E)-a-benzylsulfonyl chalcone derivatives as potential BRAF inhibitors. Eur J Med Chem. 2012;50:288–295. doi: 10.1016/j.ejmech.2012.02.007
   PubMed Web of Science ®Google Scholar
• Aiebchun T, Mahalapbutr P, Auepattanapong A, et al. Identification of vinyl sulfone derivatives as EGFR tyrosine kinase inhibitor: in vitro and in silico studies. Molecules. 2021;26(8):2211. doi: 10.3390/molecules26082211
   PubMed Web of Science ®Google Scholar
• Long Y, Yu M, Li P, et al. Synthesis and biological evaluation of heteroaryl styryl sulfone derivatives as anticancer agents. Bioorg Med Chem Lett. 2016;26(23):5674–5678. doi: 10.1016/j.bmcl.2016.10.062
   PubMed Web of Science ®Google Scholar
• Shen Y, Zificsak CA, Shea JE, et al. Design, synthesis, and biological evaluation of sulfonyl acrylonitriles as novel inhibitors of cancer metastasis and spread. J Med Chem. 2015;58(3):1140–1158. doi: 10.1021/jm501437v
   PubMed Web of Science ®Google Scholar
• Zhang J, Wang X, Chen Q, et al. (E)-β-trifluoromethyl vinylsulfones as antitumor agents: synthesis and biological evaluations. Eur J Med Chem. 2022;232:114197. doi: 10.1016/j.ejmech.2022.114197
   PubMed Web of Science ®Google Scholar
• Corcoran RB. A single inhibitor for all KRAS mutations. Nat Cancer. 2023;4(8):1060–1062. doi: 10.1038/s43018-023-00615-x
   PubMedGoogle Scholar
• Ostrem JML, Shokat KM. Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design. Nat Rev Drug Discov. 2016;15(11):771–785. doi: 10.1038/nrd.2016.139
   PubMed Web of Science ®Google Scholar
• Punekar SR, Velcheti V, Neel BG, et al. The current state of the art and future trends in RAS-targeted cancer therapies. Nat Rev Clin Oncol. 2022;19(10):637–655. doi: 10.1038/s41571-022-00671-9
   PubMed Web of Science ®Google Scholar
• Chen H, Small JB, Liu T, et al. Small-molecule inhibitors directly targeting KRAS as anticancer therapeutics. J Med Chem. 2020;63(23):14404–14424. doi: 10.1021/acs.jmedchem.0c01312
   PubMed Web of Science ®Google Scholar
• Boike L, Henning NJ, Nomura DK. Advances in covalent drug discovery. Nat Rev Drug Discov. 2022;21(12):881–898. doi: 10.1038/s41573-022-00542-z
   PubMed Web of Science ®Google Scholar
• Baillie TA. Targeted covalent inhibitors for dug design. Angew Chem Int Ed. 2016;55(43):13408–13421. doi: 10.1002/anie.201601091
   PubMed Web of Science ®Google Scholar
• Singh J. The ascension of targeted covalent inhibitors. J Med Chem. 2022;65(8):5886–5901. doi: 10.1021/acs.jmedchem.1c02134
   PubMed Web of Science ®Google Scholar
• Pettinger J, Jones K, Cheeseman MD. Lysine-targeting covalent inhibitors. Angew Chem Int Ed. 2017;56(48):15200–15209. doi: 10.1002/anie.201707630
   PubMed Web of Science ®Google Scholar
• Anscombe E, Meschini E, Mora-Vidal R, et al. Identification and characterization of an irreversible inhibitor of CDK2. Cell Chem Bio. 2015;22(9):1159–1164. doi: 10.1016/j.chembiol.2015.07.018
   Google Scholar
• Goel S, Bergholz JS, Zhao JJ. Targeting CDK4 and CDK6 in cancer. Nat Rev Cancer. 2022;22(6):356–372. doi: 10.1038/s41568-022-00456-3
   PubMed Web of Science ®Google Scholar
• Wu T, Wu X, Xu Y, et al. A patent review of selective CDK9 inhibitors in treating cancer. Expert Opin Ther Pat. 2023;33(4):309–322. doi: 10.1080/13543776.2023.2208747
   PubMed Web of Science ®Google Scholar
• Kovalová M, Baraka JP, Mik V, et al. A patent review of cyclin-dependent kinase 7 (CDK7) inhibitors (2018-2022). Expert Opin Ther Pat. 2023;33(2):67–87. doi: 10.1080/13543776.2023.2195547
   PubMed Web of Science ®Google Scholar
• Muralikrishna A, Venkatesh BC, Padmavathi V, et al. Synthesis, antimicrobial and cytotoxic activities of sulfone linked bis heterocycles. Eur J Med Chem. 2012;54:605–614. doi: 10.1016/j.ejmech.2012.06.014
   PubMed Web of Science ®Google Scholar
• Zha GF, Wang SM, Pakesh KP, et al. Discovery of novel arylethenesulfonyl fluorides as potential candidates against methicillin-resistant of staphylococcus aureus (MRSA) for overcoming multidrug resistance of bacterial infections. Eur J Med Chem. 2019;162:364–377. doi: 10.1016/j.ejmech.2018.11.012
   PubMed Web of Science ®Google Scholar
• Vorasin O, Momphanao K, Katrun P, et al. Antibacterial activity evaluation of vinyl sulfones against global predominant methicillin-resistant staphylococcus aureus USA300. Bioorg Med Chem Lett. 2022;63:128652. doi: 10.1016/j.bmcl.2022.128652
   PubMed Web of Science ®Google Scholar
• Coles VE, Darveau P, Zhang X, et al. Exploration of BAY 11-7082 as a potential antibiotic. ACS Infect Dis. 2022;8(1):170–182. doi: 10.1021/acsinfecdis.1c00522
   PubMed Web of Science ®Google Scholar
• Zhou Y, Vedantham P, Lu K, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 2015;116:76–84. doi: 10.1016/j.antiviral.2015.01.011
   PubMed Web of Science ®Google Scholar
• Mellott DM, Tseng CT, Drelich A, et al. A clinical-stage cysteine protease inhibitor blocks SARS-CoV‑2 infection of human and monkey cells. ACS Chem Biol. 2021;16(4):642–650. doi: 10.1021/acschembio.0c00875
   PubMed Web of Science ®Google Scholar
• Zhang H, Harmon M, Radoshitzky SR, et al. Vinyl sulfone-based inhibitors of nonstructural protein 2 block the replication of Venezuelan equine encephalitis virus. ACS Med Chem Lett. 2020;11(11):2139–2145. doi: 10.1021/acsmedchemlett.0c00215
   PubMed Web of Science ®Google Scholar
• Olson OC, Joyce JA. Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat Rev Cancer. 2015;15(12):712–729. doi: 10.1038/nrc4027
   PubMed Web of Science ®Google Scholar
• Verma S, Dixit R, Pandey KC. Cysteine proteases: modes of activation and future prospects as pharmacological targets. Front Pharmacol. 2016;7:107. doi: 10.3389/fphar.2016.00107
   PubMed Web of Science ®Google Scholar
• Palmer JT, Rasnick D, Klaus JL, et al. Vinyl sulfones as mechanism-based cysteine protease inhibitors. J Med Chem. 1995;38(17):3193–3196. doi: 10.1021/jm00017a002
   PubMed Web of Science ®Google Scholar
• Ettari R, Nizi E, Francesco MED, et al. Development of peptidomimetics with a vinyl sulfone warhead as irreversible falcipain-2 inhibitors. J Med Chem. 2008;51(4):988–996. doi: 10.1021/jm701141u
   PubMed Web of Science ®Google Scholar
• Zhang H, Collins J, Nyamwihura S, et al. Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent. Bioorg Med Chem Lett. 2018;28(9):1647–1651. doi: 10.1016/j.bmcl.2018.03.039
   PubMed Web of Science ®Google Scholar
• Zhang H, Collins J, Nyamwihura S, et al. Vinyl sulfone-based inhibitors of trypanosomal cysteine protease rhodesain with improved antitrypanosomal activities. Bioorg Med Chem Lett. 2020;30(14):127217. doi: 10.1016/j.bmcl.2020.127217
   PubMed Web of Science ®Google Scholar
• Glória PMC, Gut J, Gonçalves LM, et al. Aza vinyl sulfones: Synthesis and evaluation as antiplasmodial agents. Bioorg Med Chem. 2011;19(24):7635–7642. doi: 10.1016/j.bmc.2011.10.018
   PubMed Web of Science ®Google Scholar
• Oliveira R, Newton AS, Guedes RC, et al. An endoperoxide-based hybrid approach to deliver falcipain inhibitors inside malaria parasites. ChemMedchem. 2013;8(9):1528–1536. doi: 10.1002/cmdc.201300202
   PubMed Web of Science ®Google Scholar
• Engel JC, Doyle PS, Hsien I, et al. Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med. 1998;188(4):725–734. doi: 10.1084/jem.188.4.725
   PubMed Web of Science ®Google Scholar
• Doyle PS, Zhou YM, Engel JC, et al. A cysteine protease inhibitor cures Chagas disease in an immunodeficient-mouse model of infection. Antimicrob Agents Chemother. 2007;51(11):3932–3939. doi: 10.1128/AAC.00436-07
   PubMed Web of Science ®Google Scholar
• Barr SC, Warner KL, Kornreic BG, et al. A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi. Antimicrob Agents Chemother. 2005;49(12):5160–5161. doi: 10.1128/AAC.49.12.5160-5161.2005
   PubMed Web of Science ®Google Scholar
• Bogyo M, McMaster JS, Gaczynska M, et al. Covalent modification of the active site threonine of proteasomal β subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc Natl Acad Sci, USA. 1997;94(13):6629–6634. doi: 10.1073/pnas.94.13.6629
   PubMed Web of Science ®Google Scholar
• World Health Organization (2022). World Malaria Report 2021. https://www.who.int/teams/global-malaria-programme/reports/world-malariareport- 2021.
   Google Scholar
• Uwimana A, Legrand E, Stokes BH, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020;26(10):1602–1608. doi: 10.1038/s41591-020-1005-2
   PubMed Web of Science ®Google Scholar
• Uwimana A, Umulisa N, Venkatesan M, et al. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: an open-label, single- arm, multicentre, therapeutic efficacy study. Lancet Infect Dis. 2021;21(8):1120–1128. doi: 10.1016/S1473-3099(21)00142-0
   PubMed Web of Science ®Google Scholar
• Straimer J, Gandhi P, Renner KC, et al. High prevalence of Plasmodium falciparum K13 mutations in Rwanda is associated with slow parasite clearance after treatment with artemether-lumefantrine. J Infect Dis. 2022;225(8):1411–1414. doi: 10.1093/infdis/jiab352
   PubMed Web of Science ®Google Scholar
• Li H, O’Donoghue AJ, Van der Linden VA, et al. Structure- and function-based design of Plasmodium-selective proteasome inhibitors. Nature. 2016;530(7589):233–236. doi: 10.1038/nature16936
   PubMed Web of Science ®Google Scholar
• Deni I, Stokes BH, Ward KE, et al. Mitigating the risk of antimalarial resistance via covalent dual-subunit inhibition of the Plasmodium proteasome. Cell Chem Bio. 2023;30(5):470–485. doi: 10.1016/j.chembiol.2023.03.002
   PubMed Web of Science ®Google Scholar
• Bennett JM, Ward KE, Muir R, et al. Covalent macrocyclic proteasome inhibitors mitigate resistance in Plasmodium falciparum. ACS Infect Dis. 2023;9(10):2036–2047. doi: 10.1021/acsinfecdis.3c00310
   PubMed Web of Science ®Google Scholar
• Liu T, Zhang L, Joo D, et al. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2(1):e17023. doi: 10.1038/sigtrans.2017.23
   PubMed Web of Science ®Google Scholar
• Pierce JW, Schoenleber R, Jesmok G, et al. Novel inhibitors of cytokine-induced IκBa phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Bio Chem. 1997;272(34):21096–21103. doi: 10.1074/jbc.272.34.21096
   PubMed Web of Science ®Google Scholar
• Mangan MS, Olhava EJ, Roush WR, et al. Targeting the NLRP3 inflammasome in inflammatory disease. Nat Rev Drug Discov. 2018;17(8):588–606. doi: 10.1038/nrd.2018.97
   PubMed Web of Science ®Google Scholar
• Juliana C, Fernandes-Alnemri T, Wu J, et al. Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J Bio Chem. 2010;285(13):9792–9802. doi: 10.1074/jbc.M109.082305
   PubMed Web of Science ®Google Scholar
• Lee J, Rhee MH, Kim E, et al. BAY 11-7082 is a broad-spectrum inhibitor with anti-inflammatory activity against multiple targets. Mediators Inflammation. 2012;2012:416036. doi: 10.1155/2012/416036
   PubMed Web of Science ®Google Scholar
• Zhang X, Xu A, Ran Y, et al. Design, synthesis and biological evaluation of phenyl vinyl sulfone based NLRP3 inflammasome inhibitors. Bioorg Chem. 2022;128:106010. doi: 10.1016/j.bioorg.2022.106010
   PubMed Web of Science ®Google Scholar
• Cores A, Piquero M, Villacampa M, et al. NRF2 regulation processes as a source of potential drug targets against neurodegenerative diseases. Biomolecules. 2020;10(6):904. doi: 10.3390/biom10060904
   PubMed Web of Science ®Google Scholar
• Brandes MS, Gray NE. NRF2 as a therapeutic target in neurodegenerative diseases. ASN Neuro. 2020;12. doi: 10.1177/1759091419899782
   Web of Science ®Google Scholar
• Suzen S, Tucci P, Profumo E, et al. A pivotal role of Nrf2 in neurodegenerative disorders: a new way for therapeutic strategies. Pharmaceuticals. 2022;15(6):692. doi: 10.3390/ph15060692
   Web of Science ®Google Scholar
• Woo SY, Kim JH, Moon MK, et al. Discovery of vinyl sulfones as a novel class of neuroprotective agents toward Parkinson’s disease therapy. J Med Chem. 2014;57(4):1473–1487. doi: 10.1021/jm401788m
   PubMed Web of Science ®Google Scholar
• Song ZL, Hou Y, Bai F, et al. Generation of potent Nrf2 activators via tuning the electrophilicity and steric hindrance of vinyl sulfones for neuroprotection. Bioorg Chem. 2021;107:104520. doi: 10.1016/j.bioorg.2020.104520
   PubMed Web of Science ®Google Scholar
• Choi JW, Kim S, Park JH, et al. Optimization of vinyl sulfone derivatives as potent nuclear factor erythroid 2‑related factor 2 (Nrf2) activators for Parkinson’s disease therapy. J Med Chem. 2019;62(2):811–830. doi: 10.1021/acs.jmedchem.8b01527
   PubMed Web of Science ®Google Scholar
• Choi JW, Kim S, Yoo JS, et al. Development and optimization of halogenated vinyl sulfones as Nrf2 activators for the treatment of Parkinson’s disease. Eur J Med Chem. 2021;212:113103. doi: 10.1016/j.ejmech.2020.113103
   PubMed Web of Science ®Google Scholar
• Choi JW, Shin SJ, Kim HJ, et al. Antioxidant, anti-inflammatory, and neuroprotective effects of novel vinyl sulfonate compounds as Nrf2 activator. ACS Med Chem Let. 2019;10(7):1061–1067. doi: 10.1021/acsmedchemlett.9b00163
   PubMed Web of Science ®Google Scholar
• Chen YJ, Shiao MS, Wang SY. The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells. Anticancer Drugs. 2001;12(2):143–149. doi: 10.1097/00001813-200102000-00008
   PubMed Web of Science ®Google Scholar
• Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996;20(7):933–956. doi: 10.1016/0891-5849(95)02227-9
   PubMed Web of Science ®Google Scholar
• Ning X, Guo Y, Wang X, et al. Design, synthesis, and biological evaluation of (E)‑3,4- dihydroxystyryl aralkyl sulfones and sulfoxides as novel multifunctional neuroprotective agents. J Med Chem. 2014;57(10):4302–4312. doi: 10.1021/jm500258v
   PubMed Web of Science ®Google Scholar
• Chen Y, Wu B, Han Y, et al. Structure-activity relationship studies of (E)-3,4-dihydroxystyryl alkyl sulfones as novel neuroprotective agents based on improved antioxidant, anti-inflammatory activities and BBB permeability. Eur J Med Chem. 2019;171:420–433. doi: 10.1016/j.ejmech.2019.03.044
   PubMed Web of Science ®Google Scholar
• Ning X, Guo Y, Ma X, et al. Design, synthesis and pharmacological evaluation of (E)-3, 4-dihydroxy styryl sulfonamides derivatives as multifunctional neuroprotective agents against oxidative and inflammatory injury. Bioorg Med Chem. 2013;21(17):5589–5597. doi: 10.1016/j.bmc.2013.05.043
   PubMed Web of Science ®Google Scholar
• Ning X, Yuan M, Guo Y, et al. Neuroprotective effects of (E)-3, 4-diacetoxystyryl sulfone and sulfoxide derivatives in vitro models of Parkinson’s disease. J Enzyme Inhib Med Chem. 2016;31(3):464–469. doi: 10.3109/14756366.2015.1037750
   PubMed Web of Science ®Google Scholar
• Ghosh SP, Kulkarni S, Perkins MW, et al. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by ex-RAD in mice. J Radiat Res. 2012;53(4):526–536. doi: 10.1093/jrr/rrs001
   PubMed Web of Science ®Google Scholar
• Ghosh SP, Perkins MW, Hieber K, et al. Radiation protection by a new chemical entity, ex-Rad™: efficacy and mechanisms. Radiat Res. 2009;171(2):173–179. doi: 10.1667/RR1367.1
   PubMed Web of Science ®Google Scholar
• Kang AD, Cosenza SC, Bonagura M, et al. ON01210.Na (ex-RAD®) mitigates radiation damage through activation of the AKT pathway. PLoS One. 2013;8(3):e58355. doi: 10.1371/journal.pone.0058355
   PubMed Web of Science ®Google Scholar
• Chen S, Lovell S, Lee S, et al. Identification of highly selective covalent inhibitors by phage display. Nat Biotechnol 2021;39:490–498.doi: 10.1038/s41587-020-0733-7
   PubMed Web of Science ®Google Scholar
• Pan S, Jang SY, Liew SS, et al. A vinyl sulfone-based fluorogenic probe capable of selective labeling of PHGDH in live mammalian cells. Angew Chem Int Ed. 2018;57(2):579–583. doi: 10.1002/anie.201710856
   PubMed Web of Science ®Google Scholar
• Petri L, Ábrányi-Balogh P, Vagrys D, et al. A covalent strategy to target intrinsically disordered proteins: discovery of novel tau aggregation inhibitors. Eur J Med Chem. 2022;231:114163. doi: 10.1016/j.ejmech.2022.114163
   PubMed Web of Science ®Google Scholar
• Gao Y, Sun Y, Fang X, et al. Development of on-DNA vinyl sulfone synthesis for DNA-encoded chemical libraries. Org Chem Front. 2022;9(17):4542–4548. doi: 10.1039/D2QO00881E
   Web of Science ®Google Scholar
• Hewings DS, Heideker J, Ma TP, et al. Reactive-site-centric chemoproteomics identifies a distinct class of deubiquitinase enzymes. Nat Commun. 2018;9(1):1162. doi: 10.1038/s41467-018-03511-6
   PubMedGoogle Scholar
• Monfort-Vengut A, Cárcer G. Lights and shadows on the cancer multi-target inhibitor Rigosertib (ON-01910.Na). Pharmaceuticals. 2023;15(4):1232. doi: 10.3390/pharmaceutics15041232
   Google Scholar
• Prasad A, Khudaynazar N, Tantravahi RV, et al. On 01910.Na (rigosertib) inhibits PI3K/Akt pathway and activates oxidative stress signals in head and neck cancer cell lines. Oncotarget. 2016;7:79388–79400. doi: 10.18632/oncotarget.12692
   PubMedGoogle Scholar
• Gumireddy K, Reddy MVR, Cosenza SC, et al. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell. 2005;7(3):275–286. doi: 10.1016/j.ccr.2005.02.009
   PubMed Web of Science ®Google Scholar
• Komrokji RS, List AF, Wilhelm F, et al. Oral formulation of Rigosertib (ON 01910.Na) in patients with myelodysplastic syndrome (MDS)–phase I study results. Blood. 2011;118(21):3797. doi: 10.1182/blood.V118.21.3797.3797
   Web of Science ®Google Scholar
• Ogura M, Kobayashi Y, Kubonishi S, et al. Safety, efficacy, and pharmacokinetic profiles of intravenous Rigosertib in Japanese patients with recurrent/relapsed or refractory myelodysplastic syndromes: a multicenter, open-label phase I clinical study. Blood. 2016;128(22):5549. doi: 10.1182/blood.V128.22.5549.5549
   Web of Science ®Google Scholar