Skip to content
2000
image of Recent Advances in Medicinal Chemistry of Phosphodiesterase 7 Inhibitors and their Potential Therapeutic Applications

Abstract

Introduction

Phosphodiesterase 7 (PDE7) is a key enzyme in the PDE superfamily responsible for degrading cyclic adenosine monophosphate (cAMP) in pro-inflammatory and immunomodulatory cells. Elevated PDE7 activity is associated with inflammatory processes and various diseases. Suppression of PDE7 raises cAMP levels, reducing mucous secretion, cellular inflammation, and airway obstruction. This review provides an overview of the role of PDE7 in inflammatory disorders and highlights recent advances in the development of selective PDE7 inhibitors for therapeutic applications.

Methods

The review consolidates findings on the structure-activity relationships of PDE7 inhibitors. Key structural classes of small molecule inhibitors, including quinazolinone derivatives, thiadiazines, pyrimidines, and others, are discussed alongside preclinical and clinical data on selective inhibitors such as BRL50481 and OMS527.

Results

Selective PDE7 inhibitors have shown exposed potential in animal models to reduce cAMP degradation, leading to decreased inflammation and airway obstruction. BRL50481 remains the only commercially available selective PDE7 inhibitor, while OMS527 has progressed to clinical trials, demonstrating promise in treating inflammatory, neurological disorders, and leukemias.

Conclusion

Selective PDE7 inhibitors represent a novel therapeutic class for inflammatory and neurodegenerative diseases. Further research is characterised by immune dysregulation.

Loading

Article metrics loading...

/content/journals/raiad/10.2174/0127722708362767250410094814
2025-04-24
2025-10-09
Loading full text...

Full text loading...

References

  1. Punchard N.A. Whelan C.J. Adcock I. The journal of inflammation. J. Inflamm. 2004 1 1 1 10.1186/1476‑9255‑1‑1 15813979
    [Google Scholar]
  2. Chen L. Deng H. Cui H. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2018 9 6 7204 7218 10.18632/oncotarget.23208 29467962
    [Google Scholar]
  3. Nathan C. Ding A. Nonresolving inflammation. Cell 2010 140 6 871 882 10.1016/j.cell.2010.02.029 20303877
    [Google Scholar]
  4. Stone W.L. Basit H. Zubair M. Pathology, Inflammation. StatPearls. Treasure Island, FL StatPearls Publishing 2024
    [Google Scholar]
  5. Germolec D.R. Shipkowski K.A. Frawley R.P. Evans E. Markers of Inflammation. Methods Mol. Biol. 2018 1803 57 79 10.1007/978‑1‑4939‑8549‑4_5 29882133
    [Google Scholar]
  6. Roe K. An inflammation classification system using cytokine parameters. Scand. J. Immunol. 2021 93 2 e12970 10.1111/sji.12970 32892387
    [Google Scholar]
  7. Barnes P.J. Corticosteroids: The drugs to beat. Eur. J. Pharmacol. 2006 533 1-3 2 14 10.1016/j.ejphar.2005.12.052 16436275
    [Google Scholar]
  8. Crofford L.J. Use of NSAIDs in treating patients with arthritis. Arthritis Res. Ther. 2013 15 Suppl. 3 S2 24267197
    [Google Scholar]
  9. Ahmed S. NSAIDs: Chemistry and pharmacological actions. Am J Pharm Ed 2003 67 6
    [Google Scholar]
  10. Tai F.W.D. McAlindon M.E. Non-steroidal anti-inflammatory drugs and the gastrointestinal tract. Clin. Med. 2021 21 2 131 134 10.7861/clinmed.2021‑0039 33762373
    [Google Scholar]
  11. Bjarnason I. Gastrointestinal safety of NSAIDs and over-the-counter analgesics. Int. J. Clin. Pract. Suppl. 2013 178 37 42
    [Google Scholar]
  12. Laine L. GI risk and risk factors of NSAIDs. J. Cardiovasc. Pharmacol. 2006 47 Suppl. 1 S60 S66 10.1097/00005344‑200605001‑00011 16785831
    [Google Scholar]
  13. Sostres C. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res. Ther. 2013 15 Suppl. 3 S3 10.1186/ar4175 24267289
    [Google Scholar]
  14. Hawkey C.J. NSAIDs, coxibs, and the intestine. J. Cardiovasc. Pharmacol. 2006 47 Suppl. 1 S72 S75 10.1097/00005344‑200605001‑00013 16785834
    [Google Scholar]
  15. Regula J. Prevention of NSAID-associated gastrointestinal lesions: A comparison study pantoprazole versus omeprazole. Am. J. Gastroenterol. 2006 101 8 1747 1755 10.1111/j.1572‑0241.2006.00686.x 16817839
    [Google Scholar]
  16. Scheiman J.M. NSAID-induced gastrointestinal injury: A focused update for clinicians. J. Clin. Gastroenterol. 2016 50 1 5 10 10.1097/MCG.0000000000000432 26524151
    [Google Scholar]
  17. Jankowska A. Swierczek A. Chlon-Rzepa G. Pawlowski M. Wyska E. PDE7-selective and dual inhibitors: Advances in chemical and biological research. Curr. Med. Chem. 2017 24 7 673 700 10.2174/0929867324666170116125159 28093982
    [Google Scholar]
  18. Miller M. Phosphodiesterase inhibition in the treatment of autoimmune and inflammatory diseases: Current status and potential. J. Receptor Ligand Channel Res. 2014 8 19 30 10.2147/JRLCR.S50401
    [Google Scholar]
  19. Matera M.G. Ora J. Cavalli F. Rogliani P. Cazzola M. New avenues for phosphodiesterase inhibitors in asthma. J. Exp. Pharmacol. 2021 13 291 302 10.2147/JEP.S242961 33758554
    [Google Scholar]
  20. Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific therapeutic agents. Pharmacol. Ther. 2006 109 3 366 398 10.1016/j.pharmthera.2005.07.003 16102838
    [Google Scholar]
  21. Banner K.H. Page C.P. Theophylline and selective phosphodiesterase inhibitors as anti-inflammatory drugs in the treatment of bronchial asthma. Eur. Respir. J. 1995 8 6 996 1000 10.1183/09031936.95.08060996 7589387
    [Google Scholar]
  22. Essayan D.M. Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem. Pharmacol. 1999 57 9 965 973 10.1016/S0006‑2952(98)00331‑1 10796066
    [Google Scholar]
  23. Kumar M. Bhattacharya V. Cilostazol: A new drug in the treatment intermittent claudication. Recent Adv. Cardiovasc. Drug Discov. 2007 2 3 181 185 10.2174/157489007782418991 18221117
    [Google Scholar]
  24. Down G. Siederer S. Lim S. Daley-Yates P. Clinical pharmacology of Cilomilast. Clin. Pharmacokinet. 2006 45 3 217 233 10.2165/00003088‑200645030‑00001 16509757
    [Google Scholar]
  25. Konstantinos Hatzimouratidis Sildenafil in the treatment of erectile dysfunction: An overview of the clinical evidence. Clin. Interv. Aging 2006 1 4 403 414 10.2147/ciia.2006.1.4.403 18046917
    [Google Scholar]
  26. Huang J.X. Zhu B.L. Xu J.P. Zhou Z.Z. Advances in the development of phosphodiesterase 7 inhibitors. Eur. J. Med. Chem. 2023 250 115194 10.1016/j.ejmech.2023.115194 36796299
    [Google Scholar]
  27. Ichimura M. Kase H. A new cyclic nucleotide phosphodiesterase isozyme expressed in the T-lymphocyte cell lines. Biochem. Biophys. Res. Commun. 1993 193 3 985 990 10.1006/bbrc.1993.1722 8391815
    [Google Scholar]
  28. Michaeli T. Bloom T.J. Martins T. Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase-deficient Saccharomyces cerevisiae. J. Biol. Chem. 1993 268 17 12925 12932 10.1016/S0021‑9258(18)31474‑1 8389765
    [Google Scholar]
  29. Sasaki T. Kotera J. Yuasa K. Omori K. Identification of human PDE7B, a cAMP-specific phosphodiesterase. Biochem. Biophys. Res. Commun. 2000 271 3 575 583 10.1006/bbrc.2000.2661 10814504
    [Google Scholar]
  30. Omori K. Kotera J. Overview of PDEs and their regulation. Circ. Res. 2007 100 3 309 327 10.1161/01.RES.0000256354.95791.f1 17307970
    [Google Scholar]
  31. Morales-Garcia J.A. Aguilar-Morante D. Hernandez-Encinas E. Silencing phosphodiesterase 7B gene by lentiviral-shRNA interference attenuates neurodegeneration and motor deficits in hemiparkinsonian mice. Neurobiol. Aging 2015 36 2 1160 1173 10.1016/j.neurobiolaging.2014.10.008 25457552
    [Google Scholar]
  32. Sasaki T. Kotera J. Omori K. Novel alternative splice variants of rat phosphodiesterase 7B showing unique tissue-specific expression and phosphorylation. Biochem. J. 2002 361 2 211 220 10.1042/bj3610211 11772393
    [Google Scholar]
  33. Han P. Zhu X. Michaeli T. Alternative splicing of the high affinity cAMP-specific phosphodiesterase (PDE7A) mRNA in human skeletal muscle and heart. J. Biol. Chem. 1997 272 26 16152 16157 10.1074/jbc.272.26.16152 9195912
    [Google Scholar]
  34. Glavas N.A. Ostenson C. Schaefer J.B. Vasta V. Beavo J.A. T cell activation up-regulates cyclic nucleotide phosphodiesterases 8A1 and 7A3. Proc. Natl. Acad. Sci. USA 2001 98 11 6319 6324 10.1073/pnas.101131098 11371644
    [Google Scholar]
  35. Zorn A. Baillie G. Phosphodiesterase 7 as a therapeutic target – Where are we now? Cell. Signal. 2023 108 110689 10.1016/j.cellsig.2023.110689 37120115
    [Google Scholar]
  36. Azevedo M.F. Faucz F.R. Bimpaki E. Clinical and molecular genetics of the phosphodiesterases (PDEs). Endocr. Rev. 2014 35 2 195 233 10.1210/er.2013‑1053 24311737
    [Google Scholar]
  37. Bloom T.J. Beavo J.A. Identification and tissue-specific expression of PDE7 phosphodiesterase splice variants. Proc. Natl. Acad. Sci. USA 1996 93 24 14188 14192 10.1073/pnas.93.24.14188 8943082
    [Google Scholar]
  38. Delhaye S. Bardoni B. Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders. Mol. Psychiatry 2021 26 9 4570 4582 10.1038/s41380‑020‑00997‑9 33414502
    [Google Scholar]
  39. Redondo M. Brea J. Perez D.I. Effect of phosphodiesterase 7 (PDE7) inhibitors in experimental autoimmune encephalomyelitis mice. Discovery of a new chemically diverse family of compounds. J. Med. Chem. 2012 55 7 3274 3284 10.1021/jm201720d 22385507
    [Google Scholar]
  40. Safavi M. Baeeri M. Abdollahi M. New methods for the discovery and synthesis of PDE7 inhibitors as new drugs for neurological and inflammatory disorders. Expert Opin. Drug Discov. 2013 8 6 733 751 10.1517/17460441.2013.787986 23570245
    [Google Scholar]
  41. Huang Y Chen Y Kang Z Li S. Inhibiting PDE7A enhances the protective effects of neural stem cells on neurodegeneration and memory deficits in sevoflurane-exposed mice. eNeuro 2021 8 4 ENEURO.0071-21.2021. 10.1523/ENEURO.0071‑21.2021 34135002
  42. Diyoke O.I. Omeje O.N. Assor K.C. Ezema C.R. Assor J.O. Cosma S. Classification of phosphodiesterases and the therapeutic effects of their inhibitors. IJSES 2018 2 9 12 15
    [Google Scholar]
  43. Zuo H. Cattani-Cavalieri I. Musheshe N. Nikolaev V.O. Schmidt M. Phosphodiesterases as therapeutic targets for respiratory diseases. Pharmacol. Ther. 2019 197 May 225 242 10.1016/j.pharmthera.2019.02.002 30759374
    [Google Scholar]
  44. Lin C.S. Xin Z.C. Lin G. Lue T.F. Phosphodiesterases as therapeutic targets. Urology 2003 61 4 685 691 10.1016/S0090‑4295(02)02439‑1 12670544
    [Google Scholar]
  45. Peng T. Gong J. Jin Y. Inhibitors of phosphodiesterase as cancer therapeutics. Eur. J. Med. Chem. 2018 150 742 756 10.1016/j.ejmech.2018.03.046 29574203
    [Google Scholar]
  46. Wei R. Zong F. Dong J. Identification of Phosphodiesterase-7A (PDE7A) as a novel target for reducing ethanol consumption in mice. Int. J. Neuropsychopharmacol. 2024 27 8 pyae032 10.1093/ijnp/pyae032 39099166
    [Google Scholar]
  47. Paterniti I. Mazzon E. Gil C. PDE 7 inhibitors: New potential drugs for the therapy of spinal cord injury. PLoS One 2011 6 1 e15937 10.1371/journal.pone.0015937 21297958
    [Google Scholar]
  48. Jones N.A. Leport M. Holand T. Phosphodiesterase (PDE) 7 in inflammatory cells from patients with asthma and COPD. Pulm. Pharmacol. Ther. 2007 20 1 60 68 10.1016/j.pupt.2005.11.010 16427796
    [Google Scholar]
  49. Martínez A. Castro A. Gil C. Benzyl derivatives of 2,1,3-benzo- and benzothieno[3,2-a]thiadiazine 2,2-dioxides: First phosphodiesterase 7 inhibitors. J. Med. Chem. 2000 43 4 683 689 10.1021/jm990382n 10691694
    [Google Scholar]
  50. Castro A. Abasolo M.I. Gil C. Segarra V. Martinez A. CoMFA of benzyl derivatives of 2,1,3-benzo and benzothieno[3,2-a]thiadiazine 2,2-dioxides: Clues for the design of phosphodiesterase 7 inhibitors. Eur. J. Med. Chem. 2001 36 4 333 338 10.1016/S0223‑5234(01)01227‑2 11461758
    [Google Scholar]
  51. Lorthiois E. Bernardelli P. Vergne F. Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 1. Bioorg. Med. Chem. Lett. 2004 14 18 4623 4626 10.1016/j.bmcl.2004.07.011 15324876
    [Google Scholar]
  52. Bernardelli P. Lorthiois E. Vergne F. Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 2: Optimization of 5,8-disubstituted derivatives. Bioorg. Med. Chem. Lett. 2004 14 18 4627 4631 10.1016/j.bmcl.2004.07.010 15324877
    [Google Scholar]
  53. Daga P.R. Doerksen R.J. Stereoelectronic properties of spiroquinazolinones in differential PDE7 inhibitory activity. J. Comput. Chem. 2008 29 12 1945 1954 10.1002/jcc.20960 18366018
    [Google Scholar]
  54. Castaño T. Wang H. Campillo N.E. Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors. ChemMedChem 2009 4 5 866 876 10.1002/cmdc.200900043 19350606
    [Google Scholar]
  55. Guo J. Watson A. Kempson J. Identification of potent pyrimidine inhibitors of phosphodiesterase 7 (PDE7) and their ability to inhibit T cell proliferation. Bioorg. Med. Chem. Lett. 2009 19 7 1935 1938 10.1016/j.bmcl.2009.02.060 19272774
    [Google Scholar]
  56. Kempson J. Fused pyrimidine based inhibitors of phosphodiesterase 7 (PDE7): Synthesis and initial structure-activity relationships. Bioorg. Med. Chem. Lett. 2005 15 7 1829 1833 10.1016/j.bmcl.2005.02.025 15780616
    [Google Scholar]
  57. Vergne F. Bernardelli P. Lorthiois E. Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 1: Design, synthesis and structure–activity relationship studies. Bioorg. Med. Chem. Lett. 2004 14 18 4607 4613 10.1016/j.bmcl.2004.07.008 15324874
    [Google Scholar]
  58. Vergne F. Bernardelli P. Lorthiois E. Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 2: Metabolism-directed optimization studies towards orally bioavailable derivatives. Bioorg. Med. Chem. Lett. 2004 14 18 4615 4621 10.1016/j.bmcl.2004.07.009 15324875
    [Google Scholar]
  59. García-Osta A. Cuadrado-Tejedor M. García-Barroso C. Oyarzábal J. Franco R. Phosphodiesterases as therapeutic targets for Alzheimer’s disease. ACS Chem. Neurosci. 2012 3 11 832 844 10.1021/cn3000907 23173065
    [Google Scholar]
  60. Kawai K. Endo Y. Asano T. Discovery of 2-(cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as a new series of potent phosphodiesterase 7 inhibitors. J. Med. Chem. 2014 57 23 9844 9854 10.1021/jm5008215 25383422
    [Google Scholar]
  61. Endo Y. Kawai K. Asano T. Discovery and SAR study of 2-(4-pyridylamino)thieno[3,2-d]pyrimidin-4(3H)-ones as soluble and highly potent PDE7 inhibitors. Bioorg. Med. Chem. Lett. 2015 25 3 649 653 10.1016/j.bmcl.2014.11.090 25529739
    [Google Scholar]
  62. Endo Y. Kawai K. Asano T. 2-(Isopropylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as selective phosphodiesterase 7 inhibitors with potent in vivo efficacy. Bioorg. Med. Chem. Lett. 2015 25 9 1910 1914 10.1016/j.bmcl.2015.03.031 25866242
    [Google Scholar]
  63. Bartolome F. de la Cueva M. Pascual C. Amyloid β-induced impairments on mitochondrial dynamics, hippocampal neurogenesis, and memory are restored by phosphodiesterase 7 inhibition. Alzheimers Res. Ther. 2018 10 1 24 10.1186/s13195‑018‑0352‑4 29458418
    [Google Scholar]
  64. Pitts W.J. Vaccaro W. Huynh T. Identification of purine inhibitors of phosphodiesterase 7 (PDE7). Bioorg. Med. Chem. Lett. 2004 14 11 2955 2958 10.1016/j.bmcl.2004.03.021 15125967
    [Google Scholar]
  65. Chłoń-Rzepa G. Jankowska A. Ślusarczyk M. Novel butanehydrazide derivatives of purine-2,6-dione as dual PDE4/7 inhibitors with potential anti-inflammatory activity: Design, synthesis and biological evaluation. Eur. J. Med. Chem. 2018 146 381 394 10.1016/j.ejmech.2018.01.068 29407965
    [Google Scholar]
  66. Smith S.J. Cieslinski L.B. Newton R. Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: In vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes. Mol. Pharmacol. 2004 66 6 1679 1689 10.1124/mol.104.002246 15371556
    [Google Scholar]
  67. Yamamoto S. Sugahara S. Ikeda K. Shimizu Y. Amelioration of collagen-induced arthritis in mice by a novel phosphodiesterase 7 and 4 dual inhibitor, YM-393059. Eur. J. Pharmacol. 2007 559 2-3 219 226 10.1016/j.ejphar.2006.11.079 17250824
    [Google Scholar]
  68. Yamamoto S. Sugahara S. Ikeda K. Shimizu Y. Pharmacological profile of a novel phosphodiesterase 7A and -4 dual inhibitor, YM-393059, on acute and chronic inflammation models. Eur. J. Pharmacol. 2006 550 1-3 166 172 10.1016/j.ejphar.2006.08.023 17010967
    [Google Scholar]
  69. Yamamoto S. Sugahara S. Naito R. The effects of a novel phosphodiesterase 7A and -4 dual inhibitor, YM-393059, on T-cell-related cytokine production in vitro and in vivo. Eur. J. Pharmacol. 2006 541 1-2 106 114 10.1016/j.ejphar.2006.05.007 16780833
    [Google Scholar]
  70. Goto M. Tanaka Y. Murakawa M. Inhibition of phosphodiesterase 7A ameliorates Concanavalin A-induced hepatitis in mice. Int. Immunopharmacol. 2009 9 11 1347 1351 10.1016/j.intimp.2009.08.002 19671449
    [Google Scholar]
  71. Goto M. Murakawa M. Kadoshima-Yamaoka K. Phosphodiesterase 7A inhibitor ASB16165 suppresses proliferation and cytokine production of NKT cells. Cell. Immunol. 2009 258 2 147 151 10.1016/j.cellimm.2009.04.005 19477436
    [Google Scholar]
  72. de Medeiros A.S. Wyman A.R. Alaamery M.A. Identification and characterization of a potent and biologically-active PDE4/7 inhibitor via fission yeast-based assays. Cell. Signal. 2017 40 73 80 10.1016/j.cellsig.2017.08.011 28867658
    [Google Scholar]
  73. Alaamery M.A. Wyman A.R. Ivey F.D. New classes of PDE7 inhibitors identified by a fission yeast-based HTS. SLAS Discov. 2010 15 4 359 367 10.1177/1087057110362100 20228279
    [Google Scholar]
  74. Kang N.S. Jhon D.J. Song J.H. Yoo S.E. Docking and 3-D QSAR studies of dual PDE4-PDE7 inhibitors. Mol. Simul. 2007 33 14 1109 1117 10.1080/08927020701630205
    [Google Scholar]
  75. Gewald R. Rueger C. Grunwald C. Egerland U. Hoefgen N. Synthesis and structure–activity relationship studies of dihydronaphthyridinediones as a novel structural class of potent and selective PDE7 inhibitors. Bioorg. Med. Chem. Lett. 2011 21 22 6652 6656 10.1016/j.bmcl.2011.09.065 21983442
    [Google Scholar]
  76. Szczypka M. Role of phosphodiesterase 7 (PDE7) in T cell activity. effects of selective PDE7 inhibitors and dual PDE4/7 Inhibitors on T cell functions. Int. J. Mol. Sci. 2020 21 17 6118 10.3390/ijms21176118 32854348
    [Google Scholar]
  77. Banerjee A. Patil S. Pawar M.Y. Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson’s disease model. Bioorg. Med. Chem. Lett. 2012 22 19 6286 6291 10.1016/j.bmcl.2012.07.077 22944118
    [Google Scholar]
  78. Grewal A.S. Lather V. Pandita D. Dalal R. Synthesis, docking and anti-inflammatory activity of triazole amine derivatives as potential phosphodiesterase-4 inhibitors. Antiinflamm. Antiallergy Agents Med. Chem. 2017 16 1 58 67 10.2174/1871523016666170616115752 28618988
    [Google Scholar]
  79. Lather V. Synthesis, docking and anti-inflammatory activity of some newer triazole derivatives as potential PDE7 inhibitors. J Med Chem Toxicol 2017 2 2 55 61
    [Google Scholar]
  80. Grewal A.S. Sharma N. Singh S. Arora S. In silico designing of novel thiazolidine-2-one derivatives as dual PDE4/7 inhibitors for inflammatory disorders. JPTRM 2017 5 2 149 162 10.15415/jptrm.2017.52010
    [Google Scholar]
  81. Smith K.S. Jinnah H.A. GPNMB and its potential role in Parkinson’s disease and other neurodegenerative disorders. Front. Neurosci. 2012 6 42 10.3389/fnins.2012.00042
    [Google Scholar]
  82. Spina M.G. The potential of PDE7 inhibitors in neurodegenerative diseases. Expert Opin. Ther. Pat. 2016 26 4 429 441 10.1517/13543776.2016.1165235
    [Google Scholar]
  83. Brenner T. The role of cAMP signaling in neuroinflammation and neurodegeneration: Novel therapeutic approaches. Neuropharmacology 2014 91 231 243 10.1016/j.neuropharm.2014.12.015
    [Google Scholar]
  84. Sharma N. PDE7 inhibitors as a potential therapeutic target for neurodegenerative diseases: Current status and perspectives. Front. Pharmacol. 2020 11 673 10.3389/fphar.2020.00673
    [Google Scholar]
  85. Miranda A.S. Phosphodiesterase-7 inhibitor as a new anti-inflammatory drug. J. Pharmacol. Exp. Ther. 2018 366 1 29 38 10.1124/jpet.118.248708 29739826
    [Google Scholar]
  86. Renner F. PDE7A inhibition and its therapeutic potential in inflammatory diseases. Pharmacol. Ther. 2017 177 1 14 10.1016/j.pharmthera.2017.02.002
    [Google Scholar]
  87. Li Y. PDE7 inhibitors: a review of patents from 2008 to 2018. Expert Opin. Ther. Pat. 2019 29 1 59 72 10.1080/13543776.2019.1552887
    [Google Scholar]
  88. Giembycz M.A. Newton R. Beyond the dogma: Novel β2-adrenoceptor signalling in the airways. Eur. Respir. J. 2015 45 5 1378 1398 10.1183/09031936.00156514 26293503
    [Google Scholar]
  89. Cheng J.M. PDE7 inhibitors as a novel therapeutic approach for respiratory diseases. Curr. Opin. Pulm. Med. 2016 22 1 70 75 10.1097/MCP.0000000000000228
    [Google Scholar]
  90. Kassel K.M. Sadeghi S. PDE7 and its potential role in respiratory diseases. Respir. Res. 2018 19 1 26 10.1186/s12931‑018‑0721‑5 29415723
    [Google Scholar]
  91. Holst J.J. Phosphodiesterase 7A inhibition for the treatment of diabetes and obesity: In vitro and in vivo studies. Diabetes Obes. Metab. 2011 13 1 23 33 10.1111/j.1463‑1326.2010.01310.x 21812892
    [Google Scholar]
  92. Vang A.G. PDE7 inhibitors and their therapeutic potential in metabolic disorders. Expert Opin. Ther. Targets 2019 23 3 211 219 10.1080/14728222.2019.1568416
    [Google Scholar]
  93. Sun Y. Therapeutic potential of PDE7 inhibitors in metabolic diseases: Advances and perspectives. Front. Endocrinol. 2020 11 125 10.3389/fendo.2020.00125
    [Google Scholar]
  94. Zhou J. Phosphodiesterase 7 inhibitors as a new class of potential anti-cancer drugs. Oncotarget 2019 10 63 6784 6798 10.18632/oncotarget.27339
    [Google Scholar]
  95. Lopez-Gresa M.P. Phosphodiesterase 7 inhibitors as a new therapeutic approach for cancer. Mol. Cancer Ther. 2015 14 3 615 622 10.1158/1535‑7163.MCT‑14‑0728
    [Google Scholar]
  96. Zoraghi R. Inhibition of PDE7 enzyme by small molecules: Potential application in cancer therapy. Mol. Pharmacol. 2013 84 3 417 428 10.1124/mol.113.086595
    [Google Scholar]
/content/journals/raiad/10.2174/0127722708362767250410094814
Loading
/content/journals/raiad/10.2174/0127722708362767250410094814
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: BRL50481 ; leukemias ; inflammatory disorders ; neurological diseases ; cAMP ; PDE7 inhibitors
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test