3',5'-Cyclic nucleotide phosphodiesterases (PDEs, 3',5'-cyclic-nucleotide 5'-nucleotidohydrolase), E.C. 3.1.4.17, catalyse the hydrolysis of a 3',5'-cyclic nucleotide (usually cyclic AMP or cyclic GMP). Isobutylmethylxanthine is a nonselective inhibitor with an IC₅₀ value in the millimolar range for all isoforms except PDE 8A, 8B and 9A. A 2',3'-cyclic nucleotide 3'-phosphodiesterase (E.C. 3.1.4.37 CNPase) activity is associated with myelin formation in the development of the CNS.

PDE1A, 1B and 1C appear to act as soluble homodimers, while PDE2A is a membrane-bound homodimer. PDE3A and PDE3B are membrane-bound.

PDE4 isoforms are essentially cyclic AMP specific. The potency of YM976 at other members of the PDE4 family has not been reported. PDE4B–D long forms are inhibited by extracellular signal-regulated kinase (ERK)-mediated phosphorylation [18-19]. PDE4A–D splice variants can be membrane-bound or cytosolic [20]. PDE4 isoforms may be labelled with [³H]rolipram.

PDE6 is a membrane-bound tetramer composed of two catalytic chains (PDE6A or PDE6C and PDE6B), an inhibitory chain (PDE6G or PDE6H) and the PDE6D chain. The enzyme is essentially cyclic GMP specific and is activated by the α-subunit of transducin (Gα_t) and inhibited by sildenafil, zaprinast and dipyridamole with potencies lower than those observed for PDE5A. Defects in PDE6B are a cause of retinitis pigmentosa and congenital stationary night blindness.

* Key recommended reading is highlighted with an asterisk

* Baillie GS, Tejeda GS, Kelly MP. (2019) Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov, 18 (10): 770-796. [PMID:31388135]

* Bolger GB. (2021) The PDE-Opathies: Diverse Phenotypes Produced by a Functionally Related Multigene Family. Trends Genet, 37 (7): 669-681. [PMID:33832760]

Das A, Durrant D, Salloum FN, Xi L, Kukreja RC. (2015) PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer. Pharmacol Ther, 147: 12-21. [PMID:25444755]

Jørgensen C, Yasmeen S, Iversen HK, Kruuse C. (2015) Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke?. J Neurol Sci, 359 (1-2): 266-74. [PMID:26671126]

Klussmann E. (2016) Protein-protein interactions of PDE4 family members - Functions, interactions and therapeutic value. Cell Signal, 28 (7): 713-8. [PMID:26498857]

Korkmaz-Icöz S, Radovits T, Szabó G. (2018) Targeting phosphodiesterase 5 as a therapeutic option against myocardial ischaemia/reperfusion injury and for treating heart failure. Br J Pharmacol, 175 (2): 223-231. [PMID:28213937]

Leal LF, Szarek E, Faucz F, Stratakis CA. (2015) Phosphodiesterase 8B and cyclic AMP signaling in the adrenal cortex. Endocrine, 50 (1): 27-31. [PMID:25971952]

Li H, Zuo J, Tang W. (2018) Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases. Front Pharmacol, 9: 1048. [PMID:30386231]

Lobo MC, Whitehurst TS, Kaar SJ, Howes OD. (2022) New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. Neurosci Biobehav Rev, 132: 324-361. [PMID:34838528]

* Lugnier C, Meyer A, Talha S, Geny B. (2020) Cyclic nucleotide phosphodiesterases: New targets in the metabolic syndrome?. Pharmacol Ther, 208: 107475. [PMID:31926200]

Mehta A, Patel BM. (2019) Therapeutic opportunities in colon cancer: Focus on phosphodiesterase inhibitors. Life Sci, 230: 150-161. [PMID:31125564]

Movsesian M. (2016) Novel approaches to targeting PDE3 in cardiovascular disease. Pharmacol Ther, 163: 74-81. [PMID:27108947]

Ntontsi P, Detta A, Bakakos P, Loukides S, Hillas G. (2019) Experimental and investigational phosphodiesterase inhibitors in development for asthma. Expert Opin Investig Drugs, 28 (3): 261-266. [PMID:30678501]

Pauls MM, Moynihan B, Barrick TR, Kruuse C, Madigan JB, Hainsworth AH, Isaacs JD. (2018) The effect of phosphodiesterase-5 inhibitors on cerebral blood flow in humans: A systematic review. J Cereb Blood Flow Metab, 38 (2): 189-203. [PMID:29256324]

Peng T, Gong J, Jin Y, Zhou Y, Tong R, Wei X, Bai L, Shi J. (2018) Inhibitors of phosphodiesterase as cancer therapeutics. Eur J Med Chem, 150: 742-756. [PMID:29574203]

* Peng T, Qi B, He J, Ke H, Shi J. (2020) Advances in the Development of Phosphodiesterase-4 Inhibitors. J Med Chem, 63 (19): 10594-10617. [PMID:32255344]

* Piazza GA, Ward A, Chen X, Maxuitenko Y, Coley A, Aboelella NS, Buchsbaum DJ, Boyd MR, Keeton AB, Zhou G. (2020) PDE5 and PDE10 inhibition activates cGMP/PKG signaling to block Wnt/β-catenin transcription, cancer cell growth, and tumor immunity. Drug Discov Today, 25 (8): 1521-1527. [PMID:32562844]

Ricciarelli R, Fedele E. (2015) Phosphodiesterase 4D: an enzyme to remember. Br J Pharmacol, 172 (20): 4785-9. [PMID:26211680]

* Samidurai A, Xi L, Das A, Iness AN, Vigneshwar NG, Li PL, Singla DK, Muniyan S, Batra SK, Kukreja RC. (2021) Role of phosphodiesterase 1 in the pathophysiology of diseases and potential therapeutic opportunities. Pharmacol Ther, 226: 107858. [PMID:33895190]

Svensson F, Bender A, Bailey D. (2018) Fragment-Based Drug Discovery of Phosphodiesterase Inhibitors. J Med Chem, 61 (4): 1415-1424. [PMID:28800229]

* Turner MJ, Abbott-Banner K, Thomas DY, Hanrahan JW. (2021) Cyclic nucleotide phosphodiesterase inhibitors as therapeutic interventions for cystic fibrosis. Pharmacol Ther, 224: 107826. [PMID:33662448]

Wahlang B, McClain C, Barve S, Gobejishvili L. (2018) Role of cAMP and phosphodiesterase signaling in liver health and disease. Cell Signal, 49: 105-115. [PMID:29902522]

Wu C, Rajagopalan S. (2016) Phosphodiesterase-4 inhibition as a therapeutic strategy for metabolic disorders. Obes Rev, 17 (5): 429-41. [PMID:26997580]

Zagorska A, Partyka A, Bucki A, Gawalskax A, Czopek A, Pawlowski M. (2018) Phosphodiesterase 10 Inhibitors - Novel Perspectives for Psychiatric and Neurodegenerative Drug Discovery. Curr Med Chem, 25 (29): 3455-3481. [PMID:29521210]

1. Akama T, Baker SJ, Zhang YK, Hernandez V, Zhou H, Sanders V, Freund Y, Kimura R, Maples KR, Plattner JJ. (2009) Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett, 19 (8): 2129-32. [PMID:19303290]

2. Alaamery MA, Wyman AR, Ivey FD, Allain C, Demirbas D, Wang L, Ceyhan O, Hoffman CS. (2010) New classes of PDE7 inhibitors identified by a fission yeast-based HTS. J Biomol Screen, 15 (4): 359-67. [PMID:20228279]

3. Albrecht W, Unger A, Bauer SM, Laufer SA. (2017) Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases. J Med Chem, 60 (13): 5290-5305. [PMID:28613871]

4. Aoki M, Kobayashi M, Ishikawa J, Saita Y, Terai Y, Takayama K, Miyata K, Yamada T. (2000) A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity. J Pharmacol Exp Ther, 295 (1): 255-60. [PMID:10991987]

5. Boess FG, Hendrix M, van der Staay FJ, Erb C, Schreiber R, van Staveren W, de Vente J, Prickaerts J, Blokland A, Koenig G. (2004) Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology, 47 (7): 1081-92. [PMID:15555642]

6. Boyle CD, Xu R, Asberom T, Chackalamannil S, Clader JW, Greenlee WJ, Guzik H, Hu Y, Hu Z, Lankin CM et al.. (2005) Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED. Bioorg Med Chem Lett, 15 (9): 2365-9. [PMID:15837326]

7. Ceyhan O, Birsoy K, Hoffman CS. (2012) Identification of biologically active PDE11-selective inhibitors using a yeast-based high-throughput screen. Chem Biol, 19 (1): 155-63. [PMID:22284362]

8. Corbin JD, Turko IV, Beasley A, Francis SH. (2000) Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. Eur J Biochem, 267 (9): 2760-7. [PMID:10785399]

9. Edmondson SD, Mastracchio A, He J, Chung CC, Forrest MJ, Hofsess S, MacIntyre E, Metzger J, O'Connor N, Patel K et al.. (2003) Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors. Bioorg Med Chem Lett, 13 (22): 3983-7. [PMID:14592490]

10. Fawcett L, Baxendale R, Stacey P, McGrouther C, Harrow I, Soderling S, Hetman J, Beavo JA, Phillips SC. (2000) Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc Natl Acad Sci USA, 97 (7): 3702-7. [PMID:10725373]

11. Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB. (1998) Isolation and characterization of PDE8A, a novel human cAMP-specific phosphodiesterase. Biochem Biophys Res Commun, 246 (3): 570-7. [PMID:9618252]

12. Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB. (1998) Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem, 273 (25): 15559-64. [PMID:9624146]

13. Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K. (1999) Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J Biol Chem, 274 (26): 18438-45. [PMID:10373451]

14. Gao J, Long L, Xu F, Feng L, Liu Y, Shi J, Gong Q. (2020) Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischaemia/reperfusion injury by inhibiting glycogen synthase kinase-3β-mediated activation of autophagy. Br J Pharmacol, 177 (6): 1434-1452. [PMID:31658364]

15. Gardner C, Robas N, Cawkill D, Fidock M. (2000) Cloning and characterization of the human and mouse PDE7B, a novel cAMP-specific cyclic nucleotide phosphodiesterase. Biochem Biophys Res Commun, 272 (1): 186-92. [PMID:10872825]

16. Hayashi M, Matsushima K, Ohashi H, Tsunoda H, Murase S, Kawarada Y, Tanaka T. (1998) Molecular cloning and characterization of human PDE8B, a novel thyroid-specific isozyme of 3',5'-cyclic nucleotide phosphodiesterase. Biochem Biophys Res Commun, 250 (3): 751-6. [PMID:9784418]

17. Helal CJ, Arnold E, Boyden T, Chang C, Chappie TA, Fisher E, Hajos M, Harms JF, Hoffman WE, Humphrey JM et al.. (2018) Identification of a Potent, Highly Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor Clinical Candidate. J Med Chem, 61 (3): 1001-1018. [PMID:29293004]

18. Hoffmann R, Baillie GS, MacKenzie SJ, Yarwood SJ, Houslay MD. (1999) The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. EMBO J, 18 (4): 893-903. [PMID:10022832]

19. Hoffmann R, Wilkinson IR, McCallum JF, Engels P, Houslay MD. (1998) cAMP-specific phosphodiesterase HSPDE4D3 mutants which mimic activation and changes in rolipram inhibition triggered by protein kinase A phosphorylation of Ser-54: generation of a molecular model. Biochem J, 333 ( Pt 1): 139-49. [PMID:9639573]

20. Houslay MD, Adams DR. (2003) PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization. Biochem J, 370 (Pt 1): 1-18. [PMID:12444918]

21. Hughes RO, Walker JK, Rogier DJ, Heasley SE, Blevis-Bal RM, Benson AG, Jacobsen EJ, Cubbage JW, Fobian YM, Owen DR et al.. (2009) Optimization of the aminopyridopyrazinones class of PDE5 inhibitors: discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one. Bioorg Med Chem Lett, 19 (17): 5209-13. [PMID:19631533]

22. Jones GH, Venuti MC, Alvarez R, Bruno JJ, Berks AH, Prince A. (1987) Inhibitors of cyclic AMP phosphodiesterase. 1. Analogues of cilostamide and anagrelide. J Med Chem, 30 (2): 295-303. [PMID:3027338]

23. Khammy MM, Dalsgaard T, Larsen PH, Christoffersen CT, Clausen D, Rasmussen LK, Folkersen L, Grunnet M, Kehler J, Aalkjaer C et al.. (2017) PDE1A inhibition elicits cGMP-dependent relaxation of rat mesenteric arteries. Br J Pharmacol, 174 (22): 4186-4198. [PMID:28910498]

24. Kodimuthali A, Jabaris SS, Pal M. (2008) Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease. J Med Chem, 51 (18): 5471-89. [PMID:18686943]

25. Li P, Zheng H, Zhao J, Zhang L, Yao W, Zhu H, Beard JD, Ida K, Lane W, Snell G et al.. (2016) Discovery of Potent and Selective Inhibitors of Phosphodiesterase 1 for the Treatment of Cognitive Impairment Associated with Neurodegenerative and Neuropsychiatric Diseases. J Med Chem, 59 (3): 1149-64. [PMID:26789933]

26. Loughney K, Martins TJ, Harris EA, Sadhu K, Hicks JB, Sonnenburg WK, Beavo JA, Ferguson K. (1996) Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases. J Biol Chem, 271 (2): 796-806. [PMID:8557689]

27. Lunniss CJ, Cooper AW, Eldred CD, Kranz M, Lindvall M, Lucas FS, Neu M, Preston AG, Ranshaw LE, Redgrave AJ et al.. (2009) Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration. Bioorg Med Chem Lett, 19 (5): 1380-5. [PMID:19195882]

28. Martinez GR, Walker KA, Hirschfeld DR, Bruno JJ, Yang DS, Maloney PJ. (1992) 3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase. J Med Chem, 35 (4): 620-8. [PMID:1311763]

29. Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. (2014) Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov, 13 (4): 290-314. [PMID:24687066]

30. Meanwell NA, Pearce BC, Roth HR, Smith EC, Wedding DL, Wright JJ, Buchanan JO, Baryla UM, Gamberdella M, Gillespie E et al.. (1992) Inhibitors of blood platelet cAMP phosphodiesterase. 2. Structure-activity relationships associated with 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones substituted with functionalized side chains. J Med Chem, 35 (14): 2672-87. [PMID:1321910]

31. Michaeli T, Bloom TJ, Martins T, Loughney K, Ferguson K, Riggs M, Rodgers L, Beavo JA, Wigler M. (1993) Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase-deficient Saccharomyces cerevisiae. J Biol Chem, 268 (17): 12925-32. [PMID:8389765]

32. Michie AM, Lobban M, Müller T, Harnett MM, Houslay MD. (1996) Rapid regulation of PDE-2 and PDE-4 cyclic AMP phosphodiesterase activity following ligation of the T cell antigen receptor on thymocytes: analysis using the selective inhibitors erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) and rolipram. Cell Signal, 8 (2): 97-110. [PMID:8730511]

33. Mochida H, Takagi M, Inoue H, Noto T, Yano K, Fujishige K, Sasaki T, Yuasa K, Kotera J, Omori K et al.. (2002) Enzymological and pharmacological profile of T-0156, a potent and selective phosphodiesterase type 5 inhibitor. Eur J Pharmacol, 456 (1-3): 91-8. [PMID:12450574]

34. Mohamed HA, Girgis NM, Wilcken R, Bauer MR, Tinsley HN, Gary BD, Piazza GA, Boeckler FM, Abadi AH. (2011) Synthesis and molecular modeling of novel tetrahydro-β-carboline derivatives with phosphodiesterase 5 inhibitory and anticancer properties. J Med Chem, 54 (2): 495-509. [PMID:21189023]

35. Okada M, Kato M, Sato N, Uno T, Kitagaki H, Haruta J, Hiyama H, Shibata T. (2007) Oxazole compound and pharmaceutical composition. Patent number: WO2007058338. Assignee: Otsuka Pharmaceutical Co., Ltd.. Priority date: 24/05/2007. Publication date: 15/11/2005.

36. Perry MJ, O'Connell J, Walker C, Crabbe T, Baldock D, Russell A, Lumb S, Huang Z, Howat D, Allen R et al.. (1998) CDP840: a novel inhibitor of PDE-4. Cell Biochem Biophys, 29: 113-32. [PMID:9631241]

37. Rawson DJ, Ballard S, Barber C, Barker L, Beaumont K, Bunnage M, Cole S, Corless M, Denton S, Ellis D et al.. (2012) The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics. Bioorg Med Chem, 20 (1): 498-509. [PMID:22100260]

38. Saldou N, Obernolte R, Huber A, Baecker PA, Wilhelm R, Alvarez R, Li B, Xia L, Callan O, Su C et al.. (1998) Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell Signal, 10 (6): 427-40. [PMID:9720765]

39. Sasaki T, Kotera J, Yuasa K, Omori K. (2000) Identification of human PDE7B, a cAMP-specific phosphodiesterase. Biochem Biophys Res Commun, 271 (3): 575-83. [PMID:10814504]

40. Schafer PH, Parton A, Capone L, Cedzik D, Brady H, Evans JF, Man HW, Muller GW, Stirling DI, Chopra R. (2014) Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cell Signal, 26 (9): 2016-29. [PMID:24882690]

41. Sircar I, Steffen RP, Bobowski G, Burke SE, Newton RS, Weishaar RE, Bristol JA, Evans DB. (1989) Cardiotonic agents. 9. Synthesis and biological evaluation of a series of (E)-4,5-dihydro-6-[2-[4-(1H-imidazol-1-yl)phenyl]ethenyl]-3 (2H)-pyridazinones: a novel class of compounds with positive inotropic, antithrombotic, and vasodilatory activities for the treatment of congestive heart failure. J Med Chem, 32 (2): 342-50. [PMID:2536438]

42. Smith SJ, Cieslinski LB, Newton R, Donnelly LE, Fenwick PS, Nicholson AG, Barnes PJ, Barnette MS, Giembycz MA. (2004) 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, 66 (6): 1679-89. [PMID:15371556]

43. Sudo T, Tachibana K, Toga K, Tochizawa S, Inoue Y, Kimura Y, Hidaka H. (2000) Potent effects of novel anti-platelet aggregatory cilostamide analogues on recombinant cyclic nucleotide phosphodiesterase isozyme activity. Biochem Pharmacol, 59 (4): 347-56. [PMID:10644042]

44. Turko IV, Ballard SA, Francis SH, Corbin JD. (1999) Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) by sildenafil and related compounds. Mol Pharmacol, 56 (1): 124-30. [PMID:10385692]

45. Vemulapalli S, Watkins RW, Chintala M, Davis H, Ahn HS, Fawzi A, Tulshian D, Chiu P, Chatterjee M, Lin CC et al.. (1996) Antiplatelet and antiproliferative effects of SCH 51866, a novel type 1 and type 5 phosphodiesterase inhibitor. J Cardiovasc Pharmacol, 28 (6): 862-9. [PMID:8961086]

46. Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, Marr ES, Menniti FS, Nelson F, O'Connor R et al.. (2009) Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia. J Med Chem, 52 (16): 5188-96. [PMID:19630403]

47. Wang G, Liu Z, Chen T, Wang Z, Yang H, Zheng M, Ren J, Tian G, Yang X, Li L et al.. (2012) Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as novel inhibitors of PDE5. J Med Chem, 55 (23): 10540-50. [PMID:23137303]

48. Wang P, Myers JG, Wu P, Cheewatrakoolpong B, Egan RW, Billah MM. (1997) Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D. Biochem Biophys Res Commun, 234 (2): 320-4. [PMID:9177268]

49. Wu Y, Tian YJ, Le ML, Zhang SR, Zhang C, Huang MX, Jiang MY, Zhang B, Luo HB. (2020) Discovery of Novel Selective and Orally Bioavailable Phosphodiesterase-1 Inhibitors for the Efficient Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem, 63 (14): 7867-7879. [PMID:32603117]

50. You T, Cheng Y, Zhong J, Bi B, Zeng B, Zheng W, Wang H, Xu J. (2017) Roflupram, a Phosphodiesterase 4 Inhibitior, Suppresses Inflammasome Activation through Autophagy in Microglial Cells. ACS Chem Neurosci, 8 (11): 2381-2392. [PMID:28605578]

51. Zhang X, Dong G, Li H, Chen W, Li J, Feng C, Gu Z, Zhu F, Zhang R, Li M et al.. (2019) Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. J Med Chem, 62 (11): 5579-5593. [PMID:31099559]

Chen Yan, Ph.D. University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box CVRI Rochester, NY 14642