ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Crystal Structure of Human Phosphodiesterase 3B:  Atomic Basis for Substrate and Inhibitor Specificity

View Author Information
Departments of Medicinal Chemistry and Metabolic Disorders, Merck & Co., Rahway, New Jersey 07065, and MRL San Diego Neuroscience Center, San Diego, California 92121
Cite this: Biochemistry 2004, 43, 20, 6091–6100
Publication Date (Web):April 27, 2004
https://doi.org/10.1021/bi049868i
Copyright © 2004 American Chemical Society

    Article Views

    2068

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options

    Abstract

    Phosphodiesterases (PDEs) are enzymes that modulate cyclic nucleotide signaling and as such are clinical targets for a range of disorders including congestive heart failure, erectile dysfunction, and inflammation. The PDE3 family comprises two highly homologous subtypes expressed in different tissues, and inhibitors of this family have been shown to increase lipolysis in adipocytes. A specific PDE3B (the lipocyte-localized subtype) inhibitor would be a very useful tool to evaluate the effects of PDE3 inhibition on lipolysis and metabolic rate and might become a novel tool for treatment of obesity. We report here the three-dimensional structures of the catalytic domain of human PDE3B in complex with a generic PDE inhibitor and a novel PDE3 selective inhibitor. These structures explain the dual cAMP/cGMP binding capabilities of PDE3, provide the molecular basis for inhibitor specificity, and can supply a valid platform for the design of improved compounds.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

     The facilities at IMCA-CAT are supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with the Illinois Institute of Technology (IIT), executed through IIT's Center for Synchrotron Radiation Research and Instrumentation. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract No. W-31-109-Eng-38.

    *

     To whom correspondence should be addressed. Tel:  732-595-8429. Fax:  732-594-5042. E-mail:  [email protected].

     Department of Medicinal Chemistry, Merck & Co..

    §

     Department of Metabolic Disorders, Merck & Co..

     MRL San Diego Neuroscience Center.

    Cited By

    This article is cited by 99 publications.

    1. Ann M. Rowley, Gang Yao, Logan Andrews, Aaron Bedermann, Ross Biddulph, Ryan Bingham, Jennifer J. Brady, Rachel Buxton, Ted Cecconie, Rona Cooper, Adam Csakai, Enoch N. Gao, Melissa C. Grenier-Davies, Meghan Lawler, Yiqian Lian, Justyna Macina, Colin Macphee, Lisa Marcaurelle, John Martin, Patricia McCormick, Rekha Pindoria, Martin Rauch, Warren Rocque, Yingnian Shen, Lisa M. Shewchuk, Michael Squire, Will Stebbeds, Westley Tear, Xin Wang, Paris Ward, Shouhua Xiao. Discovery and SAR Study of Boronic Acid-Based Selective PDE3B Inhibitors from a Novel DNA-Encoded Library. Journal of Medicinal Chemistry 2024, 67 (3) , 2049-2065. https://doi.org/10.1021/acs.jmedchem.3c01562
    2. Nicholas A. Meanwell. Anagrelide: A Clinically Effective cAMP Phosphodiesterase 3A Inhibitor with Molecular Glue Properties. ACS Medicinal Chemistry Letters 2023, 14 (4) , 350-361. https://doi.org/10.1021/acsmedchemlett.3c00092
    3. Qing Tang, Alex M. Aronov, David D. Deininger, Simon Giroux, David J. Lauffer, Pan Li, Jianglin Liang, Kira McGinty, Steven Ronkin, Rebecca Swett, Nathan Waal, Diane Boucher, Pamella J. Ford, Cameron S. Moody. Discovery of Potent, Selective Triazolothiadiazole-Containing c-Met Inhibitors. ACS Medicinal Chemistry Letters 2021, 12 (6) , 955-960. https://doi.org/10.1021/acsmedchemlett.1c00094
    4. Gary Tresadern, Ingrid Velter, Andrés A. Trabanco, Frans Van den Keybus, Gregor J. Macdonald, Marijke V. F. Somers, Greet Vanhoof, Philip M. Leonard, Marieke B. A. C. Lamers, Yves E. M. Van Roosbroeck, Peter J. J. A. Buijnsters. [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration. Journal of Medicinal Chemistry 2020, 63 (21) , 12887-12910. https://doi.org/10.1021/acs.jmedchem.0c01272
    5. Chao-Ming Hsieh, Chun-Yi Chen, Ji-Wang Chern, Nei-Li Chan. Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting α-Helix Backbone Oxygen by Halogen Bonding. Journal of Medicinal Chemistry 2020, 63 (15) , 8485-8494. https://doi.org/10.1021/acs.jmedchem.0c00853
    6. Xiaoqing Feng, Huanchen Wang, Mengchun Ye, Xue-Tao Xu, Ying Xu, Wenzhe Yang, Han-Ting Zhang, Guoqiang Song, Hengming Ke. Identification of a PDE4-Specific Pocket for the Design of Selective Inhibitors. Biochemistry 2018, 57 (30) , 4518-4525. https://doi.org/10.1021/acs.biochem.8b00336
    7. Ian M. Robertson, Sandra E. Pineda-Sanabria, Ziqian Yan, Thomas Kampourakis, Yin-Biao Sun, Brian D. Sykes, and Malcolm Irving . Reversible Covalent Binding to Cardiac Troponin C by the Ca2+-Sensitizer Levosimendan. Biochemistry 2016, 55 (43) , 6032-6045. https://doi.org/10.1021/acs.biochem.6b00758
    8. Chimed Jansen, Albert J. Kooistra, Georgi K. Kanev, Rob Leurs, Iwan J. P. de Esch, and Chris de Graaf . PDEStrIAn: A Phosphodiesterase Structure and Ligand Interaction Annotated Database As a Tool for Structure-Based Drug Design. Journal of Medicinal Chemistry 2016, 59 (15) , 7029-7065. https://doi.org/10.1021/acs.jmedchem.5b01813
    9. Zhe Li, Yinuo Wu, Ling-Jun Feng, Ruibo Wu, and Hai-Bin Luo . Ab Initio QM/MM Study Shows a Highly Dissociated SN2 Hydrolysis Mechanism for the cGMP-Specific Phosphodiesterase-5. Journal of Chemical Theory and Computation 2014, 10 (12) , 5448-5457. https://doi.org/10.1021/ct500761d
    10. Zhongming Zhang and Nikolai O. Artemyev. Determinants for Phosphodiesterase 6 Inhibition by Its γ-Subunit. Biochemistry 2010, 49 (18) , 3862-3867. https://doi.org/10.1021/bi100354a
    11. Justin Kai-Chi Lau, Xiao-Bo Li and Yuen-Kit Cheng. A Substrate Selectivity and Inhibitor Design Lesson from the PDE10−cAMP Crystal Structure: A Computational Study. The Journal of Physical Chemistry B 2010, 114 (15) , 5154-5160. https://doi.org/10.1021/jp911156g
    12. Zahra Mashhadi, Huimin Xu and Robert H. White. An Fe2+-Dependent Cyclic Phosphodiesterase Catalyzes the Hydrolysis of 7,8-Dihydro-d-neopterin 2′,3′-Cyclic Phosphate in Methanopterin Biosynthesis. Biochemistry 2009, 48 (40) , 9384-9392. https://doi.org/10.1021/bi9010336
    13. Roya Zoraghi,, Sharron H. Francis, and, Jackie D. Corbin. Critical Amino Acids in Phosphodiesterase-5 Catalytic Site That Provide for High-Affinity Interaction with Cyclic Guanosine Monophosphate and Inhibitors. Biochemistry 2007, 46 (47) , 13554-13563. https://doi.org/10.1021/bi7010702
    14. James L. Weeks, II,, Roya Zoraghi,, Sharron H. Francis, and, Jackie D. Corbin. N-Terminal Domain of Phosphodiesterase-11A4 (PDE11A4) Decreases Affinity of the Catalytic Site for Substrates and Tadalafil, and is Involved in Oligomerization. Biochemistry 2007, 46 (36) , 10353-10364. https://doi.org/10.1021/bi7009629
    15. Qing Huai,, Yingjie Sun,, Huanchen Wang,, Dwight Macdonald,, Renée Aspiotis,, Howard Robinson,, Zheng Huang, and, Hengming Ke. Enantiomer Discrimination Illustrated by the High Resolution Crystal Structures of Type 4 Phosphodiesterase. Journal of Medicinal Chemistry 2006, 49 (6) , 1867-1873. https://doi.org/10.1021/jm051273d
    16. André Iffland,, Darcy Kohls,, Simon Low,, Jing Luan,, Yan Zhang,, Michael Kothe,, Qing Cao,, Ajith V. Kamath,, Yuan-Hua Ding, and, Tom Ellenberger. Structural Determinants for Inhibitor Specificity and Selectivity in PDE2A Using the Wheat Germ in Vitro Translation System. Biochemistry 2005, 44 (23) , 8312-8325. https://doi.org/10.1021/bi047313h
    17. David T. Manallack,, Richard A. Hughes, and, Philip E. Thompson. The Next Generation of Phosphodiesterase Inhibitors:  Structural Clues to Ligand and Substrate Selectivity of Phosphodiesterases. Journal of Medicinal Chemistry 2005, 48 (10) , 3449-3462. https://doi.org/10.1021/jm040217u
    18. Paola Gratteri,, Claudia Bonaccini, and, Fabrizio Melani. Searching for a Reliable Orientation of Ligands in Their Binding Site:  Comparison between a Structure-Based (Glide) and a Ligand-Based (FIGO) Approach in the Case Study of PDE4 Inhibitors. Journal of Medicinal Chemistry 2005, 48 (5) , 1657-1665. https://doi.org/10.1021/jm049289b
    19. Tao Liu, Anil K. Padyana, Evan T. Judd, Lei Jin, Dalia Hammoudeh, Charles Kung, Lenny Dang. Structure‐Based Design of AG‐946, a Pyruvate Kinase Activator. ChemMedChem 2024, 18 https://doi.org/10.1002/cmdc.202300559
    20. Ziyu Zhu, Wentao Tang, Xuemei Qiu, Xin Xin, Jifa Zhang. Advances in targeting Phosphodiesterase 1: From mechanisms to potential therapeutics. European Journal of Medicinal Chemistry 2024, 263 , 115967. https://doi.org/10.1016/j.ejmech.2023.115967
    21. Shabnam Pourhanafi, Vildan Adar Gürsoy. Molecular Docking, Dynamics Simulation, and Physicochemical Analysis of Some Phytochemicals as Antiplatelet Agents. Letters in Drug Design & Discovery 2023, 20 (9) , 1343-1359. https://doi.org/10.2174/1570180819666220602090408
    22. Yasukiyo YOSHIOKA, Yukiko IMI, Kyuichi KAWABATA, Katsumi SHIBATA, Junji TERAO, Noriyuki MIYOSHI. Theophylline Prevents Dexamethasone-Induced Atrophy in C2C12 Myotubes. Journal of Nutritional Science and Vitaminology 2023, 69 (4) , 284-291. https://doi.org/10.3177/jnsv.69.284
    23. Iryna V. Nizhenkovska, Kateryna V. Matskevych, Oksana I. Golovchenko, Oleksandr V. Golovchenko, Antonina D. Kustovska, Mikhaeel Van. New Prospective Phosphodiesterase Inhibitors: Phosphorylated Oxazole Derivatives in Treatment of Hypertension. Advanced Pharmaceutical Bulletin 2023, 13 (2) , 399-407. https://doi.org/10.34172/apb.2023.044
    24. Vanha N. Pham, Christopher J. Chang. Metalloallostery and Transition Metal Signaling: Bioinorganic Copper Chemistry Beyond Active Sites. Angewandte Chemie 2023, 135 (11) https://doi.org/10.1002/ange.202213644
    25. Vanha N. Pham, Christopher J. Chang. Metalloallostery and Transition Metal Signaling: Bioinorganic Copper Chemistry Beyond Active Sites. Angewandte Chemie International Edition 2023, 62 (11) https://doi.org/10.1002/anie.202213644
    26. Maria Ercu, Michael B. Mücke, Tamara Pallien, Lajos Markó, Anastasiia Sholokh, Carolin Schächterle, Atakan Aydin, Alexa Kidd, Stephan Walter, Yasmin Esmati, Brandon J. McMurray, Daniella F. Lato, Daniele Yumi Sunaga-Franze, Philip H. Dierks, Barbara Isabel Montesinos Flores, Ryan Walker-Gray, Maolian Gong, Claudia Merticariu, Kerstin Zühlke, Michael Russwurm, Tiannan Liu, Theda U.P. Batolomaeus, Sabine Pautz, Stefanie Schelenz, Martin Taube, Hanna Napieczynska, Arnd Heuser, Jenny Eichhorst, Martin Lehmann, Duncan C. Miller, Sebastian Diecke, Fatimunnisa Qadri, Elena Popova, Reika Langanki, Matthew A. Movsesian, Friedrich W. Herberg, Sofia K. Forslund, Dominik N. Müller, Tatiana Borodina, Philipp G. Maass, Sylvia Bähring, Norbert Hübner, Michael Bader, Enno Klussmann. Mutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage. Circulation 2022, 146 (23) , 1758-1778. https://doi.org/10.1161/CIRCULATIONAHA.122.060210
    27. Ilkay Erdogan Orhan, Abdur Rauf, Muhammad Saleem, Anees Ahmed Khalil. Natural Molecules as Talented Inhibitors of Nucleotide Pyrophosphatases/ Phosphodiesterases (PDEs). Current Topics in Medicinal Chemistry 2022, 22 (3) , 209-228. https://doi.org/10.2174/1568026621666210909164118
    28. Colin W. Garvie, Xiaoyun Wu, Malvina Papanastasiou, Sooncheol Lee, James Fuller, Gavin R. Schnitzler, Steven W. Horner, Andrew Baker, Terry Zhang, James P. Mullahoo, Lindsay Westlake, Stephanie H. Hoyt, Marcus Toetzl, Matthew J. Ranaghan, Luc de Waal, Joseph McGaunn, Bethany Kaplan, Federica Piccioni, Xiaoping Yang, Martin Lange, Adrian Tersteegen, Donald Raymond, Timothy A. Lewis, Steven A. Carr, Andrew D. Cherniack, Christopher T. Lemke, Matthew Meyerson, Heidi Greulich. Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-24495-w
    29. Jie Chen, Nan Liu, Yinpin Huang, Yuanxun Wang, Yuxing Sun, Qingcui Wu, Dianrong Li, Shuanhu Gao, Hong-Wei Wang, Niu Huang, Xiangbing Qi, Xiaodong Wang. Structure of PDE3A–SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-26546-8
    30. Arooma Maryam, Rana Rehan Khalid, Abdul Rauf Siddiqi, Abdulilah Ece. E-pharmacophore based virtual screening for identification of dual specific PDE5A and PDE3A inhibitors as potential leads against cardiovascular diseases. Journal of Biomolecular Structure and Dynamics 2021, 39 (7) , 2302-2317. https://doi.org/10.1080/07391102.2020.1748718
    31. Michelle Langton, Sining Sun, Chie Ueda, Max Markey, Jiahua Chen, Isaac Paddy, Paul Jiang, Natalie Chin, Amy Milne, Maria-Eirini Pandelia. The HD-Domain Metalloprotein Superfamily: An Apparent Common Protein Scaffold with Diverse Chemistries. Catalysts 2020, 10 (10) , 1191. https://doi.org/10.3390/catal10101191
    32. Ilaria Cicalini, Barbara De Filippis, Nicola Gambacorta, Antonio Di Michele, Silvia Valentinuzzi, Alessandra Ammazzalorso, Alice Della Valle, Rosa Amoroso, Orazio Nicolotti, Piero Del Boccio, Letizia Giampietro. Development of a Rapid Mass Spectrometric Determination of AMP and Cyclic AMP for PDE3 Activity Study: Application and Computational Analysis for Evaluating the Effect of a Novel 2-oxo-1,2-dihydropyridine-3-carbonitrile Derivative as PDE-3 Inhibitor. Molecules 2020, 25 (8) , 1817. https://doi.org/10.3390/molecules25081817
    33. Xiaoyun Wu, Gavin R. Schnitzler, Galen F. Gao, Brett Diamond, Andrew R. Baker, Bethany Kaplan, Kaylyn Williamson, Lindsay Westlake, Selena Lorrey, Timothy A. Lewis, Colin W. Garvie, Martin Lange, Sikander Hayat, Henrik Seidel, John Doench, Andrew D. Cherniack, Charlotte Kopitz, Matthew Meyerson, Heidi Greulich. Mechanistic insights into cancer cell killing through interaction of phosphodiesterase 3A and schlafen family member 12. Journal of Biological Chemistry 2020, 295 (11) , 3431-3446. https://doi.org/10.1074/jbc.RA119.011191
    34. Seyed Mohammad Nabavi, Sylwia Talarek, Joanna Listos, Seyed Fazel Nabavi, Kasi Pandima Devi, Marcos Roberto de Oliveira, Devesh Tewari, Sandro Argüelles, Saeed Mehrzadi, Azam Hosseinzadeh, Grazia D'onofrio, Ilkay Erdogan Orhan, Antoni Sureda, Suowen Xu, Saeedeh Momtaz, Mohammad Hosein Farzaei. Phosphodiesterase inhibitors say NO to Alzheimer's disease. Food and Chemical Toxicology 2019, 134 , 110822. https://doi.org/10.1016/j.fct.2019.110822
    35. Qing Liu, Andreas Herrmann, Qiang Huang. Surface Binding Energy Landscapes Affect Phosphodiesterase Isoform-Specific Inhibitor Selectivity. Computational and Structural Biotechnology Journal 2019, 17 , 101-109. https://doi.org/10.1016/j.csbj.2018.11.009
    36. Jessica Ostermeyer, Franziska Golly, Volkhard Kaever, Stefan Dove, Roland Seifert, Erich H. Schneider. cUMP hydrolysis by PDE3B. Naunyn-Schmiedeberg's Archives of Pharmacology 2018, 391 (9) , 891-905. https://doi.org/10.1007/s00210-018-1512-6
    37. Takakazu Mitani, Tomohide Takaya, Naoki Harada, Shigeru Katayama, Ryoichi Yamaji, Soichiro Nakamura, Hitoshi Ashida. Theophylline suppresses interleukin-6 expression by inhibiting glucocorticoid receptor signaling in pre-adipocytes. Archives of Biochemistry and Biophysics 2018, 646 , 98-106. https://doi.org/10.1016/j.abb.2018.04.001
    38. Camila Muñoz-Gutiérrez, Daniela Cáceres-Rojas, Francisco Adasme-Carreño, Iván Palomo, Eduardo Fuentes, Julio Caballero, . Docking and quantitative structure–activity relationship of bi-cyclic heteroaromatic pyridazinone and pyrazolone derivatives as phosphodiesterase 3A (PDE3A) inhibitors. PLOS ONE 2017, 12 (12) , e0189213. https://doi.org/10.1371/journal.pone.0189213
    39. Stefan Kunz, Vreni Balmer, Geert Jan Sterk, Michael P. Pollastri, Rob Leurs, Norbert Müller, Andrew Hemphill, Cornelia Spycher, . The single cyclic nucleotide-specific phosphodiesterase of the intestinal parasite Giardia lamblia represents a potential drug target. PLOS Neglected Tropical Diseases 2017, 11 (9) , e0005891. https://doi.org/10.1371/journal.pntd.0005891
    40. Lakshmi Krishnamoorthy, Joseph A Cotruvo, Jefferson Chan, Harini Kaluarachchi, Abigael Muchenditsi, Venkata S Pendyala, Shang Jia, Allegra T Aron, Cheri M Ackerman, Mark N Vander Wal, Timothy Guan, Lukas P Smaga, Samouil L Farhi, Elizabeth J New, Svetlana Lutsenko, Christopher J Chang. Copper regulates cyclic-AMP-dependent lipolysis. Nature Chemical Biology 2016, 12 (8) , 586-592. https://doi.org/10.1038/nchembio.2098
    41. João Monteiro, Marco Alves, Pedro Oliveira, Branca Silva. Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks. Molecules 2016, 21 (8) , 974. https://doi.org/10.3390/molecules21080974
    42. Bagher Alinejad, Reza Shafiee-Nick, Ahmad Ghorbani, Hamid Sadeghian. MC2, a new phosphodiesterase-3 inhibitor with antilipolytic and hypolipidemic effects in normal and diabetic rats. International Journal of Diabetes in Developing Countries 2015, 35 (4) , 408-417. https://doi.org/10.1007/s13410-015-0291-6
    43. Christos Kontogiorgis, Orazio Nicolotti, Giuseppe Felice Mangiatordi, Massimiliano Tognolini, Foteini Karalaki, Carmine Giorgio, Alexandros Patsilinakos, Angelo Carotti, Dimitra Hadjipavlou-Litina, Elisabetta Barocelli. Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry 2015, 30 (6) , 925-933. https://doi.org/10.3109/14756366.2014.995180
    44. Eleonora Corradini, Gruson Klaasse, Ulrike Leurs, Albert J. R. Heck, Nathaniel I. Martin, Arjen Scholten. Charting the interactome of PDE3A in human cells using an IBMX based chemical proteomics approach. Molecular BioSystems 2015, 11 (10) , 2786-2797. https://doi.org/10.1039/C5MB00142K
    45. Marco Conti, Wito Richter. Phosphodiesterases and Cyclic Nucleotide Signaling In The CNS. 2014, 1-46. https://doi.org/10.1002/9781118836507.ch01
    46. Frank S. Menniti, Niels Plath, Niels Svenstrup, Christopher J. Schmidt. Pharmacological Manipulation of Cyclic Nucleotide Phosphodiesterase Signaling for The Treatment of Neurological and Psychiatric Disorders In The Brain. 2014, 77-114. https://doi.org/10.1002/9781118836507.ch04
    47. Hengming Ke, Huanchen Wang, Mengchun Ye, Yingchun Huang. Crystal Structures of Phosphodiesterases and Implication on Discovery of Inhibitors. 2014, 145-170. https://doi.org/10.1002/9781118836507.ch06
    48. Jayvardhan Pandit. PDE4: New Structural Insights into the Regulatory Mechanism and Implications for the Design of Selective Inhibitors. 2014, 29-44. https://doi.org/10.1002/9783527682348.ch03
    49. Mario Di Braccio, Giancarlo Grossi, Maria Grazia Signorello, Giuliana Leoncini, Elena Cichero, Paola Fossa, Silvana Alfei, Gianluca Damonte. Synthesis, in vitro antiplatelet activity and molecular modelling studies of 10-substituted 2-(1-piperazinyl)pyrimido[1,2- a ]benzimidazol-4(10 H )-ones. European Journal of Medicinal Chemistry 2013, 62 , 564-578. https://doi.org/10.1016/j.ejmech.2013.01.026
    50. Koji Ochiai, Satoshi Takita, Akihiko Kojima, Tomohiko Eiraku, Kazuhiko Iwase, Tetsuya Kishi, Akira Ohinata, Yuichi Yageta, Tokutaro Yasue, David R. Adams, Yasushi Kohno. Phosphodiesterase inhibitors. Part 5: Hybrid PDE3/4 inhibitors as dual bronchorelaxant/anti-inflammatory agents for inhaled administration. Bioorganic & Medicinal Chemistry Letters 2013, 23 (1) , 375-381. https://doi.org/10.1016/j.bmcl.2012.08.121
    51. Ashraf Hassan Abadi, Marwa Saeed Hany, Shimaa Awadain Elsharif, Amal Abdel Haleem Eissa, Bernard DeWayne Gary, Heather Nicole Tinsley, Gary Anthony Piazza. Modulating the Cyclic Guanosine Monophosphate Substrate Selectivity of the Phosphodiesterase 3 Inhibitors by Pyridine, Pyrido[2,3-d]pyrimidine Derivatives and Their Effects upon the Growth of HT-29 Cancer Cell Line. Chemical and Pharmaceutical Bulletin 2013, 61 (4) , 405-410. https://doi.org/10.1248/cpb.c12-00993
    52. Daniella Ramos Martins, Francine Pazini, Vinícius de Medeiros Alves, Soraya Santana de Moura, Luciano Morais Lião, Mariana Torquato Quezado de Magalhães, Marize Campos Valadares, Carolina Horta Andrade, Ricardo Menegatti, Matheus Lavorenti Rocha. Synthesis, Docking Studies, Pharmacological Activity and Toxicity of a Novel Pyrazole Derivative (LQFM 021)—Possible Effects on Phosphodiesterase. Chemical and Pharmaceutical Bulletin 2013, 61 (5) , 524-531. https://doi.org/10.1248/cpb.c12-01016
    53. Justin Kai‐Chi Lau, Yuen‐Kit Cheng. An update view on the substrate recognition mechanism of phosphodiesterases: A computational study of PDE10 and PDE4 bound with cyclic nucleotides. Biopolymers 2012, 97 (11) , 910-922. https://doi.org/10.1002/bip.22104
    54. Koji Ochiai, Satoshi Takita, Akihiko Kojima, Tomohiko Eiraku, Naoki Ando, Kazuhiko Iwase, Tetsuya Kishi, Akira Ohinata, Yuichi Yageta, Tokutaro Yasue, David R. Adams, Yasushi Kohno. Phosphodiesterase inhibitors. Part 4: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-4,4-dimethylpyrazolones. Bioorganic & Medicinal Chemistry Letters 2012, 22 (18) , 5833-5838. https://doi.org/10.1016/j.bmcl.2012.07.088
    55. Koji Ochiai, Satoshi Takita, Tomohiko Eiraku, Akihiko Kojima, Kazuhiko Iwase, Tetsuya Kishi, Kazunori Fukuchi, Tokutaro Yasue, David R. Adams, Robert W. Allcock, Zhong Jiang, Yasushi Kohno. Phosphodiesterase inhibitors. Part 3: Design, synthesis and structure–activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-dihydropyridazinones with anti-inflammatory and bronchodilatory activity. Bioorganic & Medicinal Chemistry 2012, 20 (5) , 1644-1658. https://doi.org/10.1016/j.bmc.2012.01.033
    56. Sung-Jun Park, Faiyaz Ahmad, Andrew Philp, Keith Baar, Tishan Williams, Haibin Luo, Hengming Ke, Holger Rehmann, Ronald Taussig, Alexandra L. Brown, Myung K. Kim, Michael A. Beaven, Alex B. Burgin, Vincent Manganiello, Jay H. Chung. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases. Cell 2012, 148 (3) , 421-433. https://doi.org/10.1016/j.cell.2012.01.017
    57. Hilla Ovadia, Yulia Haim, Ori Nov, Orna Almog, Julia Kovsan, Nava Bashan, Moran Benhar, Assaf Rudich. Increased Adipocyte S-Nitrosylation Targets Anti-lipolytic Action of Insulin. Journal of Biological Chemistry 2011, 286 (35) , 30433-30443. https://doi.org/10.1074/jbc.M111.235945
    58. Thomas Seebeck, Geert Jan Sterk, Hengming Ke. Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite. Future Medicinal Chemistry 2011, 3 (10) , 1289-1306. https://doi.org/10.4155/fmc.11.77
    59. Robert W. Allcock, Haakon Blakli, Zhong Jiang, Karen A. Johnston, Keith M. Morgan, Georgina M. Rosair, Kazuhiko Iwase, Yasushi Kohno, David R. Adams. Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast. Bioorganic & Medicinal Chemistry Letters 2011, 21 (11) , 3307-3312. https://doi.org/10.1016/j.bmcl.2011.04.021
    60. Alexander V. Stepakov, Michail A. Kinzhalov, Vitaly M. Boitsov, Liubov V. Stepakova, Galina L. Starova, Sergey Yu. Vyazmin, Elena V. Grinenko. A new approach to the synthesis of 4-(N-aryl)carbamoylmethyl-4,5-dihydropyridazin-3(2H)-ones. Tetrahedron Letters 2011, 52 (24) , 3146-3149. https://doi.org/10.1016/j.tetlet.2011.04.038
    61. Sharron H. Francis, Mitsi A. Blount, Jackie D. Corbin. Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions. Physiological Reviews 2011, 91 (2) , 651-690. https://doi.org/10.1152/physrev.00030.2010
    62. Ki Young Kim, Hyuk Lee, Sung-Eun Yoo, Seong Hwan Kim, Nam Sook Kang. Discovery of new inhibitor for PDE3 by virtual screening. Bioorganic & Medicinal Chemistry Letters 2011, 21 (6) , 1617-1620. https://doi.org/10.1016/j.bmcl.2011.01.120
    63. Sharron H. Francis, Konjeti R. Sekhar, Hengming Ke, Jackie D. Corbin. Inhibition of Cyclic Nucleotide Phosphodiesterases by Methylxanthines and Related Compounds. 2011, 93-133. https://doi.org/10.1007/978-3-642-13443-2_4
    64. Sharron H. Francis, Miles D. Houslay, Marco Conti. Phosphodiesterase Inhibitors: Factors That Influence Potency, Selectivity, and Action. 2011, 47-84. https://doi.org/10.1007/978-3-642-17969-3_2
    65. Hengming Ke, Huanchen Wang, Mengchun Ye. Structural Insight into the Substrate Specificity of Phosphodiesterases. 2011, 121-134. https://doi.org/10.1007/978-3-642-17969-3_4
    66. Roderick E. Hubbard. Structure-based drug discovery and protein targets in the CNS. Neuropharmacology 2011, 60 (1) , 7-23. https://doi.org/10.1016/j.neuropharm.2010.07.016
    67. Tiziana Pietrangelo, Letizia Giampietro, Barbara De Filippis, Rita La Rovere, Stefania Fulle, Rosa Amoroso. Effect of milrinone analogues on intracellular calcium increase in single living H9C2 cardiac cells. European Journal of Medicinal Chemistry 2010, 45 (11) , 4928-4933. https://doi.org/10.1016/j.ejmech.2010.08.001
    68. Kelly R. Bales, Niels Plath, Niels Svenstrup, Frank S. Menniti. Phosphodiesterase Inhibition to Target the Synaptic Dysfunction in Alzheimer’s Disease. 2010, 57-90. https://doi.org/10.1007/7355_2010_8
    69. Mohsen Nikpour, Hamid Sadeghian, Mohammad Reza Saberi, Reza Shafiee Nick, Seyed Mohammad Seyedi, Azar Hosseini, Heydar Parsaee, Alireza Taghian Dasht Bozorg. Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors. Bioorganic & Medicinal Chemistry 2010, 18 (2) , 855-862. https://doi.org/10.1016/j.bmc.2009.11.044
    70. Jayvardhan Pandit, Michael D. Forman, Kimberly F. Fennell, Keith S. Dillman, Frank S. Menniti. Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct. Proceedings of the National Academy of Sciences 2009, 106 (43) , 18225-18230. https://doi.org/10.1073/pnas.0907635106
    71. Hamid Sadeghian, Seyed Mohammad Seyedi, Mohammad Reza Saberi, Reza Shafiee Nick, Azar Hosseini, Mehdi Bakavoli, Seyed Mohammad Taghi Mansouri, Heydar Parsaee. Design, synthesis and pharmacological evaluation of 6-hydroxy-4-methylquinolin-2(1H)-one derivatives as inotropic agents. Journal of Enzyme Inhibition and Medicinal Chemistry 2009, 24 (4) , 918-929. https://doi.org/10.1080/14756360802448063
    72. Jeremy M. Murray, Dirksen E. Bussiere. Targeting the Purinome. 2009, 47-92. https://doi.org/10.1007/978-1-60761-274-2_3
    73. Sharron H. Francis, Jackie D. Corbin, Erwin Bischoff. Cyclic GMP-Hydrolyzing Phosphodiesterases. 2009, 367-408. https://doi.org/10.1007/978-3-540-68964-5_16
    74. Shenping Liu, Mahmoud N. Mansour, Keith S. Dillman, Jose R. Perez, Dennis E. Danley, Paul A. Aeed, Samuel P. Simons, Peter K. LeMotte, Frank S. Menniti. Structural basis for the catalytic mechanism of human phosphodiesterase 9. Proceedings of the National Academy of Sciences 2008, 105 (36) , 13309-13314. https://doi.org/10.1073/pnas.0708850105
    75. Tasmina A. Goraya, Nanako Masada, Antonio Ciruela, Debbie Willoughby, Michael A. Clynes, Dermot M.F. Cooper. Kinetic properties of Ca2+/calmodulin-dependent phosphodiesterase isoforms dictate intracellular cAMP dynamics in response to elevation of cytosolic Ca2+. Cellular Signalling 2008, 20 (2) , 359-374. https://doi.org/10.1016/j.cellsig.2007.10.024
    76. George G. Holz, Oleg G. Chepurny, Frank Schwede. Epac-selective cAMP analogs: New tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors. Cellular Signalling 2008, 20 (1) , 10-20. https://doi.org/10.1016/j.cellsig.2007.07.009
    77. E. A. Salter, Kerrie A. O'Brien, R. Wesley Edmunds, A. Wierzbicki. ONIOM investigation of nucleotide selectivity in phosphodiesterases 3 and 4. International Journal of Quantum Chemistry 2008, 108 (6) , 1189-1199. https://doi.org/10.1002/qua.21589
    78. Huanchen Wang, Zier Yan, Jie Geng, Stefan Kunz, Thomas Seebeck, Hengming Ke. Crystal structure of the Leishmania major phosphodiesterase LmjPDEB1 and insight into the design of the parasite‐selective inhibitors. Molecular Microbiology 2007, 66 (4) , 1029-1038. https://doi.org/10.1111/j.1365-2958.2007.05976.x
    79. Francesca Spyrakis, Alessio Amadasi, Micaela Fornabaio, Donald J. Abraham, Andrea Mozzarelli, Glen E. Kellogg, Pietro Cozzini. The consequences of scoring docked ligand conformations using free energy correlations. European Journal of Medicinal Chemistry 2007, 42 (7) , 921-933. https://doi.org/10.1016/j.ejmech.2006.12.037
    80. Marco Conti, Joseph Beavo. Biochemistry and Physiology of Cyclic Nucleotide Phosphodiesterases: Essential Components in Cyclic Nucleotide Signaling. Annual Review of Biochemistry 2007, 76 (1) , 481-511. https://doi.org/10.1146/annurev.biochem.76.060305.150444
    81. Z. Huang, R. Dias, T. Jones, S. Liu, A. Styhler, D. Claveau, F. Otu, K. Ng, F. Laliberte, L. Zhang, P. Goetghebeur, W.M. Abraham, D. Macdonald, D. Dubé, M. Gallant, P. Lacombe, Y. Girard, R.N. Young, M.J. Turner, D.W. Nicholson, J.A. Mancini. L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition. Biochemical Pharmacology 2007, 73 (12) , 1971-1981. https://doi.org/10.1016/j.bcp.2007.03.010
    82. Wei Yuan, Andrés López Bernal. Cyclic AMP signalling pathways in the regulation of uterine relaxation. BMC Pregnancy and Childbirth 2007, 7 (S1) https://doi.org/10.1186/1471-2393-7-S1-S10
    83. Huanchen Wang, Yudong Liu, Jing Hou, Meiyan Zheng, Howard Robinson, Hengming Ke. Structural insight into substrate specificity of phosphodiesterase 10. Proceedings of the National Academy of Sciences 2007, 104 (14) , 5782-5787. https://doi.org/10.1073/pnas.0700279104
    84. D.P. Rotella. Phosphodiesterases. 2007, 919-957. https://doi.org/10.1016/B0-08-045044-X/00069-9
    85. Joseph A. Beavo. Phosphodiesterase 3B. 2007, 1-8. https://doi.org/10.1016/B978-008055232-3.63007-7
    86. Huanchen Wang, Hengming Ke. Structure, Catalytic Mechanism, and Inhibitor Selectivity of Cyclic Nucleotide Phosphodiesterases. 2006https://doi.org/10.1201/9781420020847.ch30
    87. Eva Degerman, Vincent Manganiello. Phosphodiesterase 3B. 2006https://doi.org/10.1201/9781420020847.ch5
    88. Kam Zhang. Crystal Structure of Phosphodiesterase Families and the Potential for Rational Drug Design. 2006https://doi.org/10.1201/9781420020847.secf
    89. Su-Hwi Hung, Wei Zhang, Robin A. Pixley, Bradford A. Jameson, Yu Chu Huang, Roberta F. Colman, Robert W. Colman. New Insights from the Structure-Function Analysis of the Catalytic Region of Human Platelet Phosphodiesterase 3A. Journal of Biological Chemistry 2006, 281 (39) , 29236-29244. https://doi.org/10.1074/jbc.M606558200
    90. Andrew T. Bender, Joseph A. Beavo. Cyclic Nucleotide Phosphodiesterases: Molecular Regulation to Clinical Use. Pharmacological Reviews 2006, 58 (3) , 488-520. https://doi.org/10.1124/pr.58.3.5
    91. Huanchen Wang, Yudong Liu, Qing Huai, Jiwen Cai, Roya Zoraghi, Sharron H. Francis, Jackie D. Corbin, Howard Robinson, Zhongcheng Xin, Guiting Lin, Hengming Ke. Multiple Conformations of Phosphodiesterase-5. Journal of Biological Chemistry 2006, 281 (30) , 21469-21479. https://doi.org/10.1074/jbc.M512527200
    92. Zheng Huang, Susana Liu, Lei Zhang, Myriam Salem, Gillian M. Greig, Chi Chung Chan, Yutaka Natsumeda, Kazuhito Noguchi. Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sciences 2006, 78 (23) , 2663-2668. https://doi.org/10.1016/j.lfs.2005.10.026
    93. N. S. Kang, C. H. Chae, S.-E. Yoo. Study on the hydrolysis mechanism of phosphodiesterase 4 using molecular dynamics simulations. Molecular Simulation 2006, 32 (5) , 369-374. https://doi.org/10.1080/08927020600717111
    94. Claire Lugnier. Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific therapeutic agents. Pharmacology & Therapeutics 2006, 109 (3) , 366-398. https://doi.org/10.1016/j.pharmthera.2005.07.003
    95. Roya Zoraghi, Jackie D. Corbin, Sharron H. Francis. Phosphodiesterase-5 Gln817 Is Critical for cGMP, Vardenafil, or Sildenafil Affinity. Journal of Biological Chemistry 2006, 281 (9) , 5553-5558. https://doi.org/10.1074/jbc.M510372200
    96. Mercedes Pozuelo Rubio, David G. Campbell, Nicholas A. Morrice, Carol Mackintosh. Phosphodiesterase 3A binds to 14-3-3 proteins in response to PMA-induced phosphorylation of Ser428. Biochemical Journal 2005, 392 (1) , 163-172. https://doi.org/10.1042/BJ20051103
    97. Francesco V. Rao, Ole A. Andersen, Kalpit A. Vora, Julie A. DeMartino, Daan M.F. van Aalten. Methylxanthine Drugs Are Chitinase Inhibitors: Investigation of Inhibition and Binding Modes. Chemistry & Biology 2005, 12 (9) , 973-980. https://doi.org/10.1016/j.chembiol.2005.07.009
    98. Huanchen Wang, Yudong Liu, Yuxiang Chen, Howard Robinson, Hengming Ke. Multiple Elements Jointly Determine Inhibitor Selectivity of Cyclic Nucleotide Phosphodiesterases 4 and 7. Journal of Biological Chemistry 2005, 280 (35) , 30949-30955. https://doi.org/10.1074/jbc.M504398200
    99. Graeme L. Card, Bruce P. England, Yoshihisa Suzuki, Daniel Fong, Ben Powell, Byunghun Lee, Catherine Luu, Maryam Tabrizizad, Sam Gillette, Prabha N. Ibrahim, Dean R. Artis, Gideon Bollag, Michael V. Milburn, Sung-Hou Kim, Joseph Schlessinger, Kam Y.J. Zhang. Structural Basis for the Activity of Drugs that Inhibit Phosphodiesterases. Structure 2004, 12 (12) , 2233-2247. https://doi.org/10.1016/j.str.2004.10.004

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect