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The 2.5 Å Crystal Structure of the SIRT1 Catalytic Domain Bound to Nicotinamide Adenine Dinucleotide (NAD+) and an Indole (EX527 Analogue) Reveals a Novel Mechanism of Histone Deacetylase Inhibition

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    The 2.5 Å Crystal Structure of the SIRT1 Catalytic Domain Bound to Nicotinamide Adenine Dinucleotide (NAD+) and an Indole (EX527 Analogue) Reveals a Novel Mechanism of Histone Deacetylase Inhibition
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    † Lilly Biotechnology Center San Diego, 10300 Campus Point Drive, Suite 200, San Diego, California 92121, United States
    ‡ Lilly Corporate Center, 355 East Merrill Street, Indianapolis, Indiana, 46285, United States
    *Phone: 858-638-8801. Fax: 858-638-889. E-mail: [email protected]
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    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2013, 56, 3, 963–969
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    https://doi.org/10.1021/jm301431y
    Published January 11, 2013
    Copyright © 2013 American Chemical Society
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    Abstract

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    The sirtuin SIRT1 is a NAD+-dependent histone deacetylase, a Sir2 family member, and one of seven human sirtuins. Sirtuins are conserved from archaea to mammals and regulate transcription, genome stability, longevity, and metabolism. SIRT1 regulates transcription via deacetylation of transcription factors such as PPARγ, NFκB, and the tumor suppressor protein p53. EX527 (27) is a nanomolar SIRT1 inhibitor and a micromolar SIRT2 inhibitor. To elucidate the mechanism of SIRT inhibition by 27, we determined the 2.5 Å crystal structure of the SIRT1 catalytic domain (residues 241–516) bound to NAD+ and the 27 analogue compound 35. 35 binds deep in the catalytic cleft, displacing the NAD+ nicotinamide and forcing the cofactor into an extended conformation. The extended NAD+ conformation sterically prevents substrate binding. The SIRT1/NAD+/35 crystal structure defines a novel mechanism of histone deacetylase inhibition and provides a basis for understanding, and rationally improving, inhibition of this therapeutically important target by drug-like molecules.

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    Thermal stability data, SPR sensograms, and electron density surrounding ligands. This material is available free of charge via the Internet at http://pubs.acs.org.

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    The atomic coordinate file has been deposited RCSB with the PDB code 4I5I.

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    36. Hemalatha Kotakommula, Vaishnavi Chintala, Satya Sree Nannapaneni, Naresh Kumar Katari, Ravikumar Kapavarapu, Manojit Pal. Wang resin catalyzed sonochemical synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines as potential inhibitors of SIRT1. Journal of Molecular Structure 2024, 1295 , 136756. https://doi.org/10.1016/j.molstruc.2023.136756
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    65. Qiufen Zhang, Yingyi Chen, Duan Ni, Zhimin Huang, Jiacheng Wei, Li Feng, Jun-Cheng Su, Yingqing Wei, Shaobo Ning, Xiuyan Yang, Mingzhu Zhao, Yuran Qiu, Kun Song, Zhengtian Yu, Jianrong Xu, Xinyi Li, Houwen Lin, Shaoyong Lu, Jian Zhang. Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells. Acta Pharmaceutica Sinica B 2022, 12 (2) , 876-889. https://doi.org/10.1016/j.apsb.2021.06.015
    66. P. Ganapathisivaraja, G. Venkata Nageswara Rao, Abburi Ramarao, Mandava Bhuvan Tej, Muthineni Sai Praneeth, Ravikumar Kapavarapu, Mandava V. Basaveswara Rao, Manojit Pal. Ultrasound assisted Cu-catalyzed decarbonylative Sonogashira coupling-cyclization strategy: Synthesis and evaluation of 3-heteroarylmethylene isoindolin-1-ones against SIRT1. Journal of Molecular Structure 2022, 1250 , 131788. https://doi.org/10.1016/j.molstruc.2021.131788
    67. Raviteja Chemboli, K.R.S. Prasad, Paritala Raghava Rao, A.V. D. Nagendra Kumar, Mandava Bhuvan Tej, Ravikumar Kapavarapu, M. V. Basaveswara Rao, Manojit Pal. Sonochemical synthesis of indolo[1,2-a]quinoxaline derivatives in the presence of Amberlyst-15: Their evaluation as potential cytotoxic agents. Journal of Molecular Structure 2022, 1250 , 131803. https://doi.org/10.1016/j.molstruc.2021.131803
    68. Yong Jung Kang, Jung Yoon Jang, Young Hoon Kwon, Jun Ho Lee, Sanggwon Lee, Yujin Park, Young-Suk Jung, Eunok Im, Hyung Ryong Moon, Hae Young Chung, Nam Deuk Kim. MHY2245, a Sirtuin Inhibitor, Induces Cell Cycle Arrest and Apoptosis in HCT116 Human Colorectal Cancer Cells. International Journal of Molecular Sciences 2022, 23 (3) , 1590. https://doi.org/10.3390/ijms23031590
    69. Li Li Ji, Dongwook Yeo. Maintenance of NAD+ Homeostasis in Skeletal Muscle during Aging and Exercise. Cells 2022, 11 (4) , 710. https://doi.org/10.3390/cells11040710
    70. Nikil Purushotham, Mrityunjay Singh, Bugga Paramesha, Vasantha Kumar, Sharad Wakode, Sanjay K. Banerjee, Boja Poojary, Shailendra Asthana. Design and synthesis of amino acid derivatives of substituted benzimidazoles and pyrazoles as Sirt1 inhibitors. RSC Advances 2022, 12 (7) , 3809-3827. https://doi.org/10.1039/D1RA06149F
    71. Li Wan, Xueying Wang, Yinghan Hu, Qing Li, Zongbao K. Zhao. Gram-scale biocatalytic preparation of the non-natural cofactor nicotinamide cytosine dinucleotide. Tetrahedron Letters 2022, 88 , 153568. https://doi.org/10.1016/j.tetlet.2021.153568
    72. Chandra Sekhar Challa, Naresh Kumar Katari, Varadacharyulu Nallanchakravarthula, Devanna Nayakanti, Ravikumar Kapavarapu, Manojit Pal. Sonochemical synthesis of 2-substituted nicotinic acid ethyl ester derivatives: Their in vitro and in silico evaluation against SIRT1. Journal of Molecular Structure 2021, 1245 , 131069. https://doi.org/10.1016/j.molstruc.2021.131069
    73. Cameron Sadegh, Wataru Ebina, Anthony C. Arvanites, Lance S. Davidow, Lee L. Rubin, Jeffrey D. Macklis, . Synthetic modified Fezf2 mRNA (modRNA) with concurrent small molecule SIRT1 inhibition enhances refinement of cortical subcerebral/corticospinal neuron identity from mouse embryonic stem cells. PLOS ONE 2021, 16 (9) , e0254113. https://doi.org/10.1371/journal.pone.0254113
    74. Nora Junker, Toni I. Gossmann. Adaptation-Driven Evolution of Sirtuin 1 (SIRT1), a Key Regulator of Metabolism and Aging, in Marmot Species. Frontiers in Ecology and Evolution 2021, 9 https://doi.org/10.3389/fevo.2021.666564
    75. Xiaoyu Duan, Weijie Sun, Hongwen Sun, Lianying Zhang. Perfluorooctane sulfonate continual exposure impairs glucose-stimulated insulin secretion via SIRT1-induced upregulation of UCP2 expression. Environmental Pollution 2021, 278 , 116840. https://doi.org/10.1016/j.envpol.2021.116840
    76. Ali A. Shati, Attalla F. El‐Kott. Acylated ghrelin protects against doxorubicin‐induced nephropathy by activating silent information regulator 1. Basic & Clinical Pharmacology & Toxicology 2021, 128 (6) , 805-821. https://doi.org/10.1111/bcpt.13569
    77. Venkata Ramana Kandula, Mohanreddy Pothireddy, K. Suresh Babu, Ravikumar Kapavarapu, Rambabu Dandela, Manojit Pal. Sonochemical synthesis of polyarylated oxazoles as potential cytotoxic agents. Tetrahedron Letters 2021, 70 , 153011. https://doi.org/10.1016/j.tetlet.2021.153011
    78. Duan Ni, Jiacheng Wei, Xinheng He, Ashfaq Ur Rehman, Xinyi Li, Yuran Qiu, Jun Pu, Shaoyong Lu, Jian Zhang. Discovery of cryptic allosteric sites using reversed allosteric communication by a combined computational and experimental strategy. Chemical Science 2021, 12 (1) , 464-476. https://doi.org/10.1039/D0SC05131D
    79. Semih Yagci, Mahmut Gozelle, Selen Gozde Kaya, Yesim Ozkan, Ahmet Bugra Aksel, Filiz Bakar-Ates, Yasemin Dundar, Gokcen Eren. Hit-to-lead optimization on aryloxybenzamide derivative virtual screening hit against SIRT. Bioorganic & Medicinal Chemistry 2021, 30 , 115961. https://doi.org/10.1016/j.bmc.2020.115961
    80. Eleni Pitsillou, Julia Liang, Andrew Hung, Tom C. Karagiannis. The circadian machinery links metabolic disorders and depression: A review of pathways, proteins and potential pharmacological interventions. Life Sciences 2021, 265 , 118809. https://doi.org/10.1016/j.lfs.2020.118809
    81. Mandava V. B. Rao, Dandamudi SriLaxmi, Suryadevara V. Vardhini, Venkata R. Guttikonda, Ravikumar Kapavarapu, Manojit Pal. Sonochemical Synthesis of 6‐Substituted Indolo[3′,2′:4,5]pyrrolo[2,3‐ b ]quinoxaline Derivatives as Potential Cytotoxic Agents. ChemistrySelect 2020, 5 (45) , 14239-14246. https://doi.org/10.1002/slct.202002951
    82. Ananth K. Vellimana, Diane J. Aum, Deepti Diwan, Julian V. Clarke, James W. Nelson, Molly Lawrence, Byung Hee Han, Jeffrey M. Gidday, Gregory J. Zipfel. SIRT1 mediates hypoxic preconditioning induced attenuation of neurovascular dysfunction following subarachnoid hemorrhage. Experimental Neurology 2020, 334 , 113484. https://doi.org/10.1016/j.expneurol.2020.113484
    83. Minna Rahnasto-Rilla, Joni Järvenpää, Marjo Huovinen, Anna-Mari Schroderus, Emmi-Leena Ihantola, Jenni Küblbeck, Mohammed Khadeer, Ruin Moaddel, Maija Lahtela-Kakkonen. Effects of galloflavin and ellagic acid on sirtuin 6 and its anti-tumorigenic activities. Biomedicine & Pharmacotherapy 2020, 131 , 110701. https://doi.org/10.1016/j.biopha.2020.110701
    84. Luke S. Hutchings‐Goetz, Chao Yang, James W. B. Fyfe, Thomas N. Snaddon. Enantioselective Syntheses of Strychnos and Chelidonium Alkaloids through Regio‐ and Stereocontrolled Cooperative Catalysis. Angewandte Chemie 2020, 132 (40) , 17709-17717. https://doi.org/10.1002/ange.202005151
    85. Luke S. Hutchings‐Goetz, Chao Yang, James W. B. Fyfe, Thomas N. Snaddon. Enantioselective Syntheses of Strychnos and Chelidonium Alkaloids through Regio‐ and Stereocontrolled Cooperative Catalysis. Angewandte Chemie International Edition 2020, 59 (40) , 17556-17564. https://doi.org/10.1002/anie.202005151
    86. Ilyes Saidi, Vijaykumar D. Nimbarte, Harald Schwalbe, Pierre Waffo-Téguo, Abdel Halim Harrath, Lamjed Mansour, Saleh Alwasel, Hichem Ben Jannet. Anti-tyrosinase, anti-cholinesterase and cytotoxic activities of extracts and phytochemicals from the Tunisian Citharexylum spinosum L.: Molecular docking and SAR analysis. Bioorganic Chemistry 2020, 102 , 104093. https://doi.org/10.1016/j.bioorg.2020.104093
    87. Hanna Laaroussi, Ying Ding, Yuou Teng, Patrick Deschamps, Michel Vidal, Peng Yu, Sylvain Broussy. Synthesis of indole inhibitors of silent information regulator 1 (SIRT1), and their evaluation as cytotoxic agents. European Journal of Medicinal Chemistry 2020, 202 , 112561. https://doi.org/10.1016/j.ejmech.2020.112561
    88. Ilyes Saidi, Wiem Baccari, Axel Marchal, Pierre Waffo-Téguo, Abdel Halim Harrath, Lamjed Mansour, Hichem Ben Jannet. Iridoid glycosides from the Tunisian Citharexylum spinosum L.: Isolation, structure elucidation, biological evaluation, molecular docking and SAR analysis. Industrial Crops and Products 2020, 151 , 112440. https://doi.org/10.1016/j.indcrop.2020.112440
    89. Lucia Scisciola, Federica Sarno, Vincenzo Carafa, Sandro Cosconati, Salvatore Di Maro, Loreta Ciuffreda, Antonella De Angelis, Paola Stiuso, Alessandra Feoli, Gianluca Sbardella, Lucia Altucci, Angela Nebbioso. Two novel SIRT1 activators, SCIC2 and SCIC2.1, enhance SIRT1-mediated effects in stress response and senescence. Epigenetics 2020, 15 (6-7) , 664-683. https://doi.org/10.1080/15592294.2019.1704349
    90. Fanbiao Meng, Minxian Qian, Bin Peng, Linyuan Peng, Xiaohui Wang, Kang Zheng, Zuojun Liu, Xiaolong Tang, Shuju Zhang, Shimin Sun, Xinyue Cao, Qiuxiang Pang, Bosheng Zhao, Wenbin Ma, Zhou Songyang, Bo Xu, Wei-Guo Zhu, Xingzhi Xu, Baohua Liu. Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice. eLife 2020, 9 https://doi.org/10.7554/eLife.55828
    91. Nicola Mautone, Clemens Zwergel, Antonello Mai, Dante Rotili. Sirtuin modulators: where are we now? A review of patents from 2015 to 2019. Expert Opinion on Therapeutic Patents 2020, 30 (6) , 389-407. https://doi.org/10.1080/13543776.2020.1749264
    92. Meng-qian Chen, Kui-wu Yao, Zhang-jing Liu, Xiao-xiao Feng, Ye Xiao. Xuefu Zhuyu Oral Liquid (血府逐瘀口服液) Prevents Apoptosis of Ischemic Myocardium Cells in Rats by Regulating SIRT1 and Its Pathway-Related Genes. Chinese Journal of Integrative Medicine 2020, 26 (6) , 442-447. https://doi.org/10.1007/s11655-019-3076-9
    93. Tanira Matutino Bastos, Milena Botelho Pereira Soares, Caio Haddad Franco, Laura Alcântara, Lorenzo Antonini, Manuela Sabatino, Nicola Mautone, Lucio Holanda Freitas-Junior, Carolina Borsoi Moraes, Rino Ragno, Dante Rotili, Sergio Schenkman, Antonello Mai, Nilmar Silvio Moretti. Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes. International Journal of Molecular Sciences 2020, 21 (10) , 3659. https://doi.org/10.3390/ijms21103659
    94. Nathalie Wössner, Zayan Alhalabi, Jessica González, Sören Swyter, Jin Gan, Karin Schmidtkunz, Lin Zhang, Alejandro Vaquero, Huib Ovaa, Oliver Einsle, Wolfgang Sippl, Manfred Jung. Sirtuin 1 Inhibiting Thiocyanates (S1th)—A New Class of Isotype Selective Inhibitors of NAD+ Dependent Lysine Deacetylases. Frontiers in Oncology 2020, 10 https://doi.org/10.3389/fonc.2020.00657
    95. Sarwat Chowdhury, Smitha Sripathy, Alyssa A. Webster, Angela Park, Uyen Lao, Joanne H. Hsu, Taylor Loe, Antonio Bedalov, Julian A. Simon. Discovery of Selective SIRT2 Inhibitors as Therapeutic Agents in B-Cell Lymphoma and Other Malignancies. Molecules 2020, 25 (3) , 455. https://doi.org/10.3390/molecules25030455
    96. Sylvain Broussy, Hanna Laaroussi, Michel Vidal. Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat). Journal of Enzyme Inhibition and Medicinal Chemistry 2020, 35 (1) , 1124-1136. https://doi.org/10.1080/14756366.2020.1758691
    97. Shuntaro Chiba, Masahito Ohue, Anastasiia Gryniukova, Petro Borysko, Sergey Zozulya, Nobuaki Yasuo, Ryunosuke Yoshino, Kazuyoshi Ikeda, Woong-Hee Shin, Daisuke Kihara, Mitsuo Iwadate, Hideaki Umeyama, Takaaki Ichikawa, Reiji Teramoto, Kun-Yi Hsin, Vipul Gupta, Hiroaki Kitano, Mika Sakamoto, Akiko Higuchi, Nobuaki Miura, Kei Yura, Masahiro Mochizuki, Chandrasekaran Ramakrishnan, A. Mary Thangakani, D. Velmurugan, M. Michael Gromiha, Itsuo Nakane, Nanako Uchida, Hayase Hakariya, Modong Tan, Hironori K. Nakamura, Shogo D. Suzuki, Tomoki Ito, Masahiro Kawatani, Kentaroh Kudoh, Sakurako Takashina, Kazuki Z. Yamamoto, Yoshitaka Moriwaki, Keita Oda, Daisuke Kobayashi, Tatsuya Okuno, Shintaro Minami, George Chikenji, Philip Prathipati, Chioko Nagao, Attayeb Mohsen, Mari Ito, Kenji Mizuguchi, Teruki Honma, Takashi Ishida, Takatsugu Hirokawa, Yutaka Akiyama, Masakazu Sekijima. A prospective compound screening contest identified broader inhibitors for Sirtuin 1. Scientific Reports 2019, 9 (1) https://doi.org/10.1038/s41598-019-55069-y
    98. Xinxin Jin, Xiaomin Kang, Liting Zhao, Mao Xu, Tianping Xie, Huixia Li, Fang Li, Zhuang Qian, Zhengmin Ma, Ying Zhang, Wei Yang, Zhuanmin Zhang, Xin Gao, Qian Chen, Hongzhi Sun, Shufang Wu. Cartilage Ablation of Sirt1 Causes Inhibition of Growth Plate Chondrogenesis by Hyperactivation of mTORC1 Signaling. Endocrinology 2019, 160 (12) , 3001-3017. https://doi.org/10.1210/en.2019-00427
    99. Ramu Manjula, Nikhila Gokhale, Sruthi Unni, Prashant Deshmukh, Rajkumar Reddyrajula, M.M. Srinivas Bharath, Udayakumar Dalimba, Balasundaram Padmanabhan. Design, synthesis, in-vitro evaluation and molecular docking studies of novel indole derivatives as inhibitors of SIRT1 and SIRT2. Bioorganic Chemistry 2019, 92 , 103281. https://doi.org/10.1016/j.bioorg.2019.103281
    100. Alessandro Maugeri, Nadia Ferlazzo, Laura De Luca, Rosaria Gitto, Michele Navarra. The link between the AMPK/SIRT1 axis and a flavonoid‐rich extract of Citrus bergamia juice: A cell‐free, in silico, and in vitro study. Phytotherapy Research 2019, 33 (7) , 1805-1814. https://doi.org/10.1002/ptr.6368
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    Cite this: J. Med. Chem. 2013, 56, 3, 963–969
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    https://doi.org/10.1021/jm301431y
    Published January 11, 2013
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