4l7d › Citations

Binding mode and structure-activity relationships around direct inhibitors of the Nrf2-Keap1 complex.

Jnoff E, Albrecht C, Barker JJ, Barker O, Beaumont E, Bromidge S, Brookfield F, Brooks M, Bubert C, Ceska T, Corden V, Dawson G, Duclos S, Fryatt T, Genicot C, Jigorel E, Kwong J, Maghames R, Mushi I, Pike R, Sands ZA, Smith MA, Stimson CC, Courade JP
ChemMedChem 9 699-705 (2014)
Related entries: 4l7b, 4l7c, 4n1b

Cited: 60 times
EuropePMC logo PMID: 24504667

Abstract

An X-ray crystal structure of Kelch-like ECH-associated protein (Keap1) co-crystallised with (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)-1 a, as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.

Reviews - 4l7d mentioned but not cited (2)

  1. Targeting Cullin-RING E3 ubiquitin ligases for drug discovery: structure, assembly and small-molecule modulation. Bulatov E, Ciulli A. Biochem J 467 365-386 (2015)
  2. KEAP1-NRF2 protein-protein interaction inhibitors: Design, pharmacological properties and therapeutic potential. Crisman E, Duarte P, Dauden E, Cuadrado A, Rodríguez-Franco MI, López MG, León R. Med Res Rev 43 237-287 (2023)

Articles - 4l7d mentioned but not cited (5)

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  3. Lipid-Based Nanoparticle Formulation of Diallyl Trisulfide Chemosensitizes the Growth Inhibitory Activity of Doxorubicin in Colorectal Cancer Model: A Novel In Vitro, In Vivo and In Silico Analysis. Alrumaihi F, Khan MA, Babiker AY, Alsaweed M, Azam F, Allemailem KS, Almatroudi AA, Ahamad SR, Alsugoor MH, Alharbi KN, Almansour NM, Khan A. Molecules 27 2192 (2022)
  4. Molecular docking and dynamics guided approach to identify potential anti-inflammatory molecules as NRF2 activator to protect against drug-induced liver injury (DILI): a computational study. Mili A, Das S, Nandakumar K, Lobo R. J Biomol Struct Dyn 1-18 (2022)
  5. A computational study to identify Sesamol derivatives as NRF2 activator for protection against drug-induced liver injury (DILI). Mili A, Birangal S, Nandakumar K, Lobo R. Mol Divers (2023)


Reviews citing this publication (20)

  1. Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development. Robledinos-Antón N, Fernández-Ginés R, Manda G, Cuadrado A. Oxid Med Cell Longev 2019 9372182 (2019)
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  12. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) drug discovery: Biochemical toolbox to develop NRF2 activators by reversible binding of Kelch-like ECH-associated protein 1 (KEAP1). Bresciani A, Missineo A, Gallo M, Cerretani M, Fezzardi P, Tomei L, Cicero DO, Altamura S, Santoprete A, Ingenito R, Bianchi E, Pacifici R, Dominguez C, Munoz-Sanjuan I, Harper S, Toledo-Sherman L, Park LC. Arch Biochem Biophys 631 31-41 (2017)
  13. Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects. Shahcheraghi SH, Salemi F, Peirovi N, Ayatollahi J, Alam W, Khan H, Saso L. Molecules 27 167 (2021)
  14. Recent progress in the development of small molecule Nrf2 modulators: a patent review (2012-2016). Sun H, Zhu J, Lin H, Gu K, Feng F. Expert Opin Ther Pat 27 763-785 (2017)
  15. Targeting NRF2 to treat cancer. Sivinski J, Zhang DD, Chapman E. Semin Cancer Biol 76 61-73 (2021)
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  17. Role of Nuclear Factor Erythroid 2 (Nrf2) in the Recovery of Long COVID-19 Using Natural Antioxidants: A Systematic Review. Muchtaridi M, Amirah SR, Harmonis JA, Ikram EHK. Antioxidants (Basel) 11 1551 (2022)
  18. Advances in Immunosuppressive Agents Based on Signal Pathway. Xu Z, Chu M. Front Pharmacol 13 917162 (2022)
  19. Targeting NLRP3 Inflammasome With Nrf2 Inducers in Central Nervous System Disorders. Tastan B, Arioz BI, Genc S. Front Immunol 13 865772 (2022)
  20. Platanosides, a Potential Botanical Drug Combination, Decrease Liver Injury Caused by Acetaminophen Overdose in Mice. Samuvel DJ, Nguyen NT, Jaeschke H, Lemasters JJ, Wang X, Choo YM, Hamann MT, Zhong Z. J Nat Prod 85 1779-1788 (2022)

Articles citing this publication (33)

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  2. Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators. Jain AD, Potteti H, Richardson BG, Kingsley L, Luciano JP, Ryuzoji AF, Lee H, Krunic A, Mesecar AD, Reddy SP, Moore TW. Eur J Med Chem 103 252-268 (2015)
  3. Nrf2 activation through the inhibition of Keap1-Nrf2 protein-protein interaction. Lee S, Hu L. Med Chem Res 29 846-867 (2020)
  4. Synthesis of Keap1-phosphorylated p62 and Keap1-Nrf2 protein-protein interaction inhibitors and their inhibitory activity. Yasuda D, Nakajima M, Yuasa A, Obata R, Takahashi K, Ohe T, Ichimura Y, Komatsu M, Yamamoto M, Imamura R, Kojima H, Okabe T, Nagano T, Mashino T. Bioorg Med Chem Lett 26 5956-5959 (2016)
  5. Hippuric Acid Promotes Renal Fibrosis by Disrupting Redox Homeostasis via Facilitation of NRF2-KEAP1-CUL3 Interactions in Chronic Kidney Disease. Sun B, Wang X, Liu X, Wang L, Ren F, Wang X, Leng X. Antioxidants (Basel) 9 E783 (2020)
  6. Investigation of Molecular Details of Keap1-Nrf2 Inhibitors Using Molecular Dynamics and Umbrella Sampling Techniques. Londhe AM, Gadhe CG, Lim SM, Pae AN. Molecules 24 E4085 (2019)
  7. Potent Natural Antioxidant Carveol Attenuates MCAO-Stress Induced Oxidative, Neurodegeneration by Regulating the Nrf-2 Pathway. Malik I, Shah FA, Ali T, Tan Z, Alattar A, Ullah N, Khan AU, Alshaman R, Li S. Front Neurosci 14 659 (2020)
  8. Polar Recognition Group Study of Keap1-Nrf2 Protein-Protein Interaction Inhibitors. Lu MC, Tan SJ, Ji JA, Chen ZY, Yuan ZW, You QD, Jiang ZY. ACS Med Chem Lett 7 835-840 (2016)
  9. Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats. Hassanein EHM, Abd El-Ghafar OAM, Ahmed MA, Sayed AM, Gad-Elrab WM, Ajarem JS, Allam AA, Mahmoud AM. Drug Des Devel Ther 14 5275-5288 (2020)
  10. Identification of Non-Electrophilic Nrf2 Activators from Approved Drugs. Zhang QY, Chu XY, Jiang LH, Liu MY, Mei ZL, Zhang HY. Molecules 22 E883 (2017)
  11. Interaction Energetics and Druggability of the Protein-Protein Interaction between Kelch-like ECH-Associated Protein 1 (KEAP1) and Nuclear Factor Erythroid 2 Like 2 (Nrf2). Zhong M, Lynch A, Muellers SN, Jehle S, Luo L, Hall DR, Iwase R, Carolan JP, Egbert M, Wakefield A, Streu K, Harvey CM, Ortet PC, Kozakov D, Vajda S, Allen KN, Whitty A. Biochemistry 59 563-581 (2020)
  12. In vivo and in vitro protective effects of shengmai injection against doxorubicin-induced cardiotoxicity. Zhou P, Gao G, Zhao CC, Li JY, Peng JF, Wang SS, Song R, Shi H, Wang L. Pharm Biol 60 638-651 (2022)
  13. Aggregate Interactome Based on Protein Cross-linking Interfaces Predicts Drug Targets to Limit Aggregation in Neurodegenerative Diseases. Balasubramaniam M, Ayyadevara S, Ganne A, Kakraba S, Penthala NR, Du X, Crooks PA, Griffin ST, Shmookler Reis RJ. iScience 20 248-264 (2019)
  14. Osthole protects against Ang II-induced endotheliocyte death by targeting NF-κB pathway and Keap-1/Nrf2 pathway. Tao L, Gu X, Xu E, Ren S, Zhang L, Liu W, Lin X, Yang J, Chen C. Am J Transl Res 11 142-159 (2019)
  15. Identification of novel indole derivatives acting as inhibitors of the Keap1-Nrf2 interaction. Cosimelli B, Greco G, Laneri S, Novellino E, Sacchi A, Amendola G, Cosconati S, Bortolozzi R, Viola G. J Enzyme Inhib Med Chem 34 1152-1157 (2019)
  16. Thermodynamic profiling of inhibitors of Nrf2:Keap1 interactions. Nasiri HR, Linge S, Ullmann D. Bioorg Med Chem Lett 26 526-529 (2016)
  17. A bioactive ligand-conjugated iridium(III) metal-based complex as a Keap1-Nrf2 protein-protein interaction inhibitor against acetaminophen-induced acute liver injury. Li G, Liu H, Feng R, Kang TS, Wang W, Ko CN, Wong CY, Ye M, Ma DL, Wan JB, Leung CH. Redox Biol 48 102129 (2021)
  18. Combined Peptide and Small-Molecule Approach toward Nonacidic THIQ Inhibitors of the KEAP1/NRF2 Interaction. Ontoria JM, Biancofiore I, Fezzardi P, Ferrigno F, Torrente E, Colarusso S, Bianchi E, Andreini M, Patsilinakos A, Kempf G, Augustin M, Steinbacher S, Summa V, Pacifici R, Muñoz-Sanjuan I, Park L, Bresciani A, Dominguez C, Sherman LT, Harper S. ACS Med Chem Lett 11 740-746 (2020)
  19. Nrf2 is crucial for the down-regulation of Cyp7a1 induced by arachidonic acid in Hepg2 cells. Zhang JM, Wang XH, Hao LH, Wang H, Zhang XY, Muhammad I, Qi Y, Li GL, Sun XQ. Environ Toxicol Pharmacol 52 21-26 (2017)
  20. Discovery of a Kelch-like ECH-associated protein 1-inhibitory tetrapeptide and its structural characterization. Sogabe S, Sakamoto K, Kamada Y, Kadotani A, Fukuda Y, Sakamoto JI. Biochem Biophys Res Commun 486 620-625 (2017)
  21. Discovery of a small molecule modulator of the Kv1.1/Kvβ1 channel complex that reduces neuronal excitability and in vitro epileptiform activity. Niespodziany I, Mullier B, André VM, Ghisdal P, Jnoff E, Moreno-Delgado D, Swinnen D, Sands Z, Wood M, Wolff C. CNS Neurosci Ther 25 442-451 (2019)
  22. Ganoderic acid targeting nuclear factor erythroid 2-related factor 2 in lung cancer. Gill BS, Kumar S, Navgeet. Tumour Biol 39 1010428317695530 (2017)
  23. Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Sulfamidate Imines: Efficient Synthesis of Chiral Cyclic Sulfamidates. Liu Y, Yi Z, Tan X, Dong XQ, Zhang X. iScience 19 63-73 (2019)
  24. High Fat Diet-Induced Hepatic 18-Carbon Fatty Acids Accumulation Up-Regulates CYP2A5/CYP2A6 via NF-E2-Related Factor 2. Wang XH, Cui XX, Sun XQ, Wang XH, Li XC, Qi Y, Li W, Han MY, Muhammad I, Zhang XY. Front Pharmacol 8 233 (2017)
  25. Identification of novel inhibitors of Keap1/Nrf2 by a promising method combining protein-protein interaction-oriented library and machine learning. Shimizu Y, Yonezawa T, Sakamoto J, Furuya T, Osawa M, Ikeda K. Sci Rep 11 7420 (2021)
  26. Vinpocetine-based therapy is an attractive strategy against oxidative stress-induced hepatotoxicity in vitro by targeting Nrf2/HO-1 pathway. Abdelmageed N, Twafik WA, Seddek AL, Morad SAF. EXCLI J 20 550-561 (2021)
  27. Activation of anti-oxidant Nrf2 signaling by substituted trans stilbenes. Deck LM, Whalen LJ, Hunsaker LA, Royer RE, Vander Jagt DL. Bioorg Med Chem 25 1423-1430 (2017)
  28. In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids. Guan T, Bian C, Ma Z. Front Nutr 10 1257172 (2023)
  29. Characterization of tangeretin as an activator of nuclear factor erythroid 2-related factor 2/antioxidant response element pathway in HEK293T cells. Lv C, Li Y, Liang R, Huang W, Xiao Y, Ma X, Wang Y, Zou H, Qin F, Sun C, Li T, Zhang J. Curr Res Food Sci 6 100459 (2023)
  30. Echinochrome Ameliorates Physiological, Immunological, and Histopathological Alterations Induced by Ovalbumin in Asthmatic Mice by Modulating the Keap1/Nrf2 Signaling Pathway. Abdelmawgood IA, Mahana NA, Badr AM, Mohamed AS, Al Shawoush AM, Atia T, Abdelrazak AE, Sakr HI. Mar Drugs 21 455 (2023)
  31. Generating Potential Protein-Protein Interaction Inhibitor Molecules Based on Physicochemical Properties. Ohue M, Kojima Y, Kosugi T. Molecules 28 5652 (2023)
  32. Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1-Nrf2 PPI Inhibitor. Otake K, Ubukata M, Nagahashi N, Ogawa N, Hantani Y, Hantani R, Adachi T, Nomura A, Yamaguchi K, Maekawa M, Mamada H, Motomura T, Sato M, Harada K. ACS Med Chem Lett 14 658-665 (2023)
  33. Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure-Activity Relationships. Zhang D, Li X, He X, Xing Y, Jiang B, Xiu Z, Bao Y, Dong Y. Molecules 27 7804 (2022)


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