Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T02001
(Former ID: TTDS00499)
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| Target Name |
Phosphodiesterase 4D (PDE4D)
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| Synonyms |
cAMP-specific 3',5'-cyclic phosphodiesterase 4D; PDE43; DPDE3
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| Gene Name |
PDE4D
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Tonus and reflex abnormality [ICD-11: MB47] | |||||
| Function |
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Click to Show/Hide
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| BioChemical Class |
Phosphoric diester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.4.53
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| Sequence |
MEAEGSSAPARAGSGEGSDSAGGATLKAPKHLWRHEQHHQYPLRQPQFRLLHPHHHLPPP
PPPSPQPQPQCPLQPPPPPPLPPPPPPPGAARGRYASSGATGRVRHRGYSDTERYLYCRA MDRTSYAVETGHRPGLKKSRMSWPSSFQGLRRFDVDNGTSAGRSPLDPMTSPGSGLILQA NFVHSQRRESFLYRSDSDYDLSPKSMSRNSSIASDIHGDDLIVTPFAQVLASLRTVRNNF AALTNLQDRAPSKRSPMCNQPSINKATITEEAYQKLASETLEELDWCLDQLETLQTRHSV SEMASNKFKRMLNRELTHLSEMSRSGNQVSEFISNTFLDKQHEVEIPSPTQKEKEKKKRP MSQISGVKKLMHSSSLTNSSIPRFGVKTEQEDVLAKELEDVNKWGLHVFRIAELSGNRPL TVIMHTIFQERDLLKTFKIPVDTLITYLMTLEDHYHADVAYHNNIHAADVVQSTHVLLST PALEAVFTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHLAVGF KLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLKTMVETKKVTSSGVL LLDNYSDRIQVLQNMVHCADLSNPTKPLQLYRQWTDRIMEEFFRQGDRERERGMEISPMC DKHNASVEKSQVGFIDYIVHPLWETWADLVHPDAQDILDTLEDNREWYQSTIPQSPSPAP DDPEEGRQGQTEKFQFELTLEEDGESDTEKDSGSQVEEDTSCSDSKTLCTQDSESTEIPL DEQVEEEAVGEEEESQPEACVIDDRSPDT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T66FP0 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Papaverine | Drug Info | Approved | Spasm | [2] | |
| Clinical Trial Drug(s) | [+] 20 Clinical Trial Drugs | + | ||||
| 1 | DENBUFYLLINE | Drug Info | Phase 3 | Cognitive impairment | [3] | |
| 2 | SOTB07 | Drug Info | Phase 3 | Asthma | [4] | |
| 3 | AN-2898 | Drug Info | Phase 2 | Atopic dermatitis | [5] | |
| 4 | AWD-12-281 | Drug Info | Phase 2 | Rhinitis | [6] | |
| 5 | BPN14770 | Drug Info | Phase 2 | Alzheimer disease | [7] | |
| 6 | CC-1088 | Drug Info | Phase 2 | Crohn disease | [8] | |
| 7 | GPD-1116 | Drug Info | Phase 2 | Asthma | [9] | |
| 8 | HT-0712 | Drug Info | Phase 2 | Cognitive impairment | [10] | |
| 9 | LIRIMILAST | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [11] | |
| 10 | MK-0873 | Drug Info | Phase 2 | Psoriasis vulgaris | [12] | |
| 11 | Oglemilast | Drug Info | Phase 2 | Asthma | [13] | |
| 12 | OX-914 | Drug Info | Phase 2 | Asthma | [14] | |
| 13 | Piclamilast | Drug Info | Phase 2 | Rheumatoid arthritis | [15] | |
| 14 | Revamilast | Drug Info | Phase 2 | Asthma | [16] | |
| 15 | TA-7906 | Drug Info | Phase 2 | Atopic dermatitis | [17] | |
| 16 | TOFIMILAST | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [18] | |
| 17 | AVE-8112 | Drug Info | Phase 1 | Parkinson disease | [19] | |
| 18 | GSK-356278 | Drug Info | Phase 1 | Huntington disease | [20] | |
| 19 | MEM-1414 | Drug Info | Phase 1 | Mood disorder | [21] | |
| 20 | Ronomilast | Drug Info | Phase 1 | Chronic obstructive pulmonary disease | [22] | |
| Discontinued Drug(s) | [+] 14 Discontinued Drugs | + | ||||
| 1 | CDP840 | Drug Info | Discontinued in Phase 2 | Chronic obstructive pulmonary disease | [23] | |
| 2 | CI-1018 | Drug Info | Discontinued in Phase 2 | Asthma | [24] | |
| 3 | Daxalipram | Drug Info | Discontinued in Phase 2 | Multiple sclerosis | [25] | |
| 4 | KW-4490 | Drug Info | Discontinued in Phase 2 | Asthma | [26] | |
| 5 | LAS-37779 | Drug Info | Discontinued in Phase 2 | Psoriasis vulgaris | [27] | |
| 6 | V-11294A | Drug Info | Discontinued in Phase 2 | Asthma | [28] | |
| 7 | D-4418 | Drug Info | Discontinued in Phase 1 | Cutaneous T-cell lymphoma | [29] | |
| 8 | SCH-351591 | Drug Info | Discontinued in Phase 1 | Chronic obstructive pulmonary disease | [30] | |
| 9 | YM-976 | Drug Info | Discontinued in Phase 1 | Asthma | [31], [32] | |
| 10 | D-22888 | Drug Info | Terminated | Allergy | [33] | |
| 11 | GW-3600 | Drug Info | Terminated | Asthma | [34] | |
| 12 | NIK-616 | Drug Info | Terminated | Chronic obstructive pulmonary disease | [35] | |
| 13 | TJN-598 | Drug Info | Terminated | Glomerulonephritis | [36] | |
| 14 | Torbafylline | Drug Info | Terminated | Peripheral vascular disease | [37] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 48 Inhibitor drugs | + | ||||
| 1 | Papaverine | Drug Info | [1] | |||
| 2 | DENBUFYLLINE | Drug Info | [38] | |||
| 3 | SOTB07 | Drug Info | [39] | |||
| 4 | AN-2898 | Drug Info | [40] | |||
| 5 | AWD-12-281 | Drug Info | [41] | |||
| 6 | BPN14770 | Drug Info | [42], [43] | |||
| 7 | CC-1088 | Drug Info | [44] | |||
| 8 | GPD-1116 | Drug Info | [9] | |||
| 9 | HT-0712 | Drug Info | [39] | |||
| 10 | LIRIMILAST | Drug Info | [45] | |||
| 11 | MK-0873 | Drug Info | [46] | |||
| 12 | Oglemilast | Drug Info | [47] | |||
| 13 | OX-914 | Drug Info | [48] | |||
| 14 | Piclamilast | Drug Info | [49] | |||
| 15 | Revamilast | Drug Info | [50] | |||
| 16 | TA-7906 | Drug Info | [51] | |||
| 17 | TOFIMILAST | Drug Info | [45] | |||
| 18 | AVE-8112 | Drug Info | [52] | |||
| 19 | GSK-356278 | Drug Info | [53] | |||
| 20 | MEM-1414 | Drug Info | [54] | |||
| 21 | Ronomilast | Drug Info | [55] | |||
| 22 | CDP840 | Drug Info | [56] | |||
| 23 | CI-1018 | Drug Info | [57] | |||
| 24 | Daxalipram | Drug Info | [58] | |||
| 25 | KW-4490 | Drug Info | [59] | |||
| 26 | LAS-37779 | Drug Info | [60] | |||
| 27 | V-11294A | Drug Info | [61] | |||
| 28 | D-4418 | Drug Info | [62] | |||
| 29 | SCH-351591 | Drug Info | [63] | |||
| 30 | YM-976 | Drug Info | [45] | |||
| 31 | GW-3600 | Drug Info | [65] | |||
| 32 | NIK-616 | Drug Info | [66] | |||
| 33 | TJN-598 | Drug Info | [36] | |||
| 34 | ZAPRINAST | Drug Info | [67] | |||
| 35 | 1-Butyl-3-methyl-3,7-dihydro-purine-2,6-dione | Drug Info | [68] | |||
| 36 | 1-Methyl-3-propyl-3,7-dihydro-purine-2,6-dione | Drug Info | [68] | |||
| 37 | ASP-3258 | Drug Info | [39] | |||
| 38 | CD-160130 | Drug Info | [39] | |||
| 39 | CHF-5480 | Drug Info | [39] | |||
| 40 | isobutylmethylxanthine | Drug Info | [1], [69] | |||
| 41 | KF-66490 | Drug Info | [70] | |||
| 42 | L-454560 | Drug Info | [71] | |||
| 43 | L-869298 | Drug Info | [72] | |||
| 44 | OCID-2987 | Drug Info | [39] | |||
| 45 | ROLIPRAM | Drug Info | [73] | |||
| 46 | RS-25344 | Drug Info | [74] | |||
| 47 | TAS-203 | Drug Info | [39] | |||
| 48 | UCB-101333-3 | Drug Info | [75] | |||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | D-22888 | Drug Info | [64] | |||
| 2 | Torbafylline | Drug Info | [37] | |||
| 3 | AL-59640 | Drug Info | [39] | |||
| 4 | CH-3697 | Drug Info | [39] | |||
| 5 | ZL-N-91 | Drug Info | [39] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | cAMP signaling pathway | |||||
| 3 | Morphine addiction | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Purine Metabolism | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | DARPP-32 events | |||||
| 2 | G alpha (s) signalling events | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | G Protein Signaling Pathways | |||||
| 2 | Myometrial Relaxation and Contraction Pathways | |||||
| 3 | TSH signaling pathway | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 2 | Drug information of Papaverine, 2008. eduDrugs. | |||||
| REF 3 | Denbufylline in dementia: a double-blind controlled study. Dement Geriatr Cogn Disord. 1999 Nov-Dec;10(6):505-10. | |||||
| REF 4 | ClinicalTrials.gov (NCT01907763) Study Phase III Study to Assess the Efficacy and Safety of SOTB07 in Asthma Patients. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01301508) Efficacy and Safety of AN2898 and AN2728 Topical Ointments to Treat Mild-to-Moderate Atopic Dermatitis. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT00354510) Topical GW842470X In Adults Patients With Moderate Atopic Dermatitis. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT03817684) Tetra PICASSO AD Trial: Study to Evaluate Effects of BPN14770 in Early Alzheimer's Subjects. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT00045786) Study to Determine the Safety and Preliminary Efficacy of CC-1088 in the Treatment of Myelodysplastic Syndromes. U.S. National Institutes of Health. | |||||
| REF 9 | Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 s... Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L196-204. | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018324) | |||||
| REF 11 | A novel phosphodiesterase 4 inhibitor template. Expert Opinion on Therapeutic Patents,2003, 13(6), 929-933. | |||||
| REF 12 | ClinicalTrials.gov (NCT00132730) An Investigational Drug Study In Patients With COPD (Chronic Obstructive Pulmonary Disease) (MK-0873-005). U.S. National Institutes of Health. | |||||
| REF 13 | ClinicalTrials.gov (NCT00671073) Study To Assess Efficacy and Safety of Oglemilast in Patients With Chronic Obstructive Pulmonary Disease (COPD). U.S. National Institutes of Health. | |||||
| REF 14 | ClinicalTrials.gov (NCT00758446) Efficacy and Safety Study of BLX-028914 in Subjects With Allergic Rhinitis. U.S. National Institutes of Health. | |||||
| REF 15 | Effect of food and gender on the pharmacokinetics of RP 73401, a phosphodiesterase IV inhibitor. Int J Clin Pharmacol Ther. 2000 Dec;38(12):588-94. | |||||
| REF 16 | ClinicalTrials.gov (NCT01436890) A Clinical Trial to Study the Effects of Revamilast in Patients With Chronic Persistent Asthma. U.S. National Institutes of Health. | |||||
| REF 17 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024588) | |||||
| REF 18 | ClinicalTrials.gov (NCT00150397) A Study of the Safety and Efficacy of Tofimilast in Adult Asthmatics. U.S. National Institutes of Health. | |||||
| REF 19 | ClinicalTrials.gov (NCT01803945) A Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AVE8112 in Patients With Parkinson's Disease. U.S. National Institutes of Health. | |||||
| REF 20 | ClinicalTrials.gov (NCT01031186) First Time in Human Study. U.S. National Institutes of Health. | |||||
| REF 21 | The Quest for Human Longevity, Lewis D. Solo. Page(145). | |||||
| REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013990) | |||||
| REF 23 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003087) | |||||
| REF 24 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010034) | |||||
| REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015672) | |||||
| REF 26 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017153) | |||||
| REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022894) | |||||
| REF 28 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012597) | |||||
| REF 29 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007757) | |||||
| REF 30 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010874) | |||||
| REF 31 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5292). | |||||
| REF 32 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010783) | |||||
| REF 33 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007179) | |||||
| REF 34 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006447) | |||||
| REF 35 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020194) | |||||
| REF 36 | Effects of TJN-598, a new selective phosphodiesterase type IV inhibitor on anti-Thy1 nephritis in rats. Clin Exp Nephrol. 2011 Feb;15(1):14-24. | |||||
| REF 37 | Phosphodiesterase (PDE) inhibitor torbafylline (HWA 448) attenuates burn-induced rat skeletal muscle proteolysis through the PDE4/cAMP/EPAC/PI3K/Akt pathway. Mol Cell Endocrinol. 2014 Aug 5;393(1-2):152-63. | |||||
| REF 38 | Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. J Med Chem. 2002 May 23;45(11):2342-5. | |||||
| REF 39 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1303). | |||||
| REF 40 | An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen. 2013 Jun;54(5):338-46. | |||||
| REF 41 | The phosphodiesterase 4 inhibitor AWD 12-281 is active in a new guinea-pig model of allergic skin inflammation predictive of human skin penetration and suppresses both Th1 and Th2 cytokines in mice. J Pharm Pharmacol. 2005 Dec;57(12):1609-17. | |||||
| REF 42 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 43 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 44 | Thalidomide analogs and PDE4 inhibition. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2669-74. | |||||
| REF 45 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 46 | MK-0873, a PDE4 inhibitor, does not influence the pharmacokinetics of theophylline in healthy male volunteers. Pulm Pharmacol Ther. 2008;21(3):573-7. | |||||
| REF 47 | Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking . Br J Pharmacol. 2008 October; 155(3): 288-290. | |||||
| REF 48 | Orexo announces Phase IIa data on OX914 in rhinitis. Orexo. 24th March, 2009. | |||||
| REF 49 | Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable COPD patients. Lung. 2004;182(6):369-77. | |||||
| REF 50 | WO patent application no. 2012,1109,46, Pharmaceutical composition comprising the pde4 enzyme inhibitor revamilast and a disease modifying agent, preferably methotrexate . | |||||
| REF 51 | Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. Clin Exp Immunol. 2002 Jun;128(3):460-6. | |||||
| REF 52 | Therapy for Parkinson's Disease: What is in the Pipeline . Neurotherapeutics. 2014 January; 11(1): 24-33. | |||||
| REF 53 | GSK356278, a potent, selective, brain-penetrant phosphodiesterase 4 inhibitor that demonstrates anxiolytic and cognition-enhancing effects without inducing side effects in preclinical species. J Pharmacol Exp Ther. 2014 Jul;350(1):153-63. | |||||
| REF 54 | The effect of the novel phosphodiesterase-4 inhibitor MEM 1414 on the allergen induced responses in mild asthma. BMC Pulm Med. 2014 Oct 28;14:166. | |||||
| REF 55 | Clinical pipeline report, company report or official report of Avarx. | |||||
| REF 56 | Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: structure-activity relationship, optimization, and identification of a highly... Bioorg Med Chem Lett. 2005 Dec 1;15(23):5241-6. | |||||
| REF 57 | New substituted triaza-benzo[cd]azulen-9-ones as promising phosphodiesterase-4 inhibitors. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3303-6. | |||||
| REF 58 | Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice. Front Neurosci. 2014 May 27;8:129. | |||||
| REF 59 | Pharmacokinetics and metabolism of KW-4490, a selective phosphodiesterase 4 inhibitor: difference in excretion of KW-4490 and acylglucuronide metabolites between rats and cynomolgus monkeys. Xenobiotica. 2008 May;38(5):511-26. | |||||
| REF 60 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022894) | |||||
| REF 61 | Pharmacokinetic and pharmacodynamic profile following oral administration of the phosphodiesterase (PDE)4 inhibitor V11294A in healthy volunteers. Br J Clin Pharmacol. 2002 Nov;54(5):478-84. | |||||
| REF 62 | Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking. Br J Pharmacol. 2008 Oct;155(3):288-90. | |||||
| REF 63 | Synthesis and profile of SCH351591, a novel PDE4 inhibitor. Bioorg Med Chem Lett. 2002 Jun 17;12(12):1621-3. | |||||
| REF 64 | Effects of a selective PDE4 inhibitor, D-22888, on human airways and eosinophils in vitro and late phase allergic pulmonary eosinophilia in guinea pigs. Pulm Pharmacol Ther. 1998 Feb;11(1):13-21. | |||||
| REF 65 | Dual inhibition of human type 4 phosphodiesterase isostates by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3- methyl-1-pyrrolidinecarboxylate. Biochemistry. 1998 May 12;37(19):6894-904. | |||||
| REF 66 | Preclinical trials in Chronic obstructive pulmonary disease in Japan (PO). 2004 | |||||
| REF 67 | 8-Substituted analogues of 3-(3-cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine: highly potent and selective PDE4 inhibitors. J Med Chem. 2005 Feb 24;48(4):1237-43. | |||||
| REF 68 | Effects of alkyl substitutions of xanthine skeleton on bronchodilation. J Med Chem. 1992 Oct 30;35(22):4039-44. | |||||
| REF 69 | A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity. J Med Chem. 1985 May;28(5):537-45. | |||||
| REF 70 | Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models. Int Immunopharmacol. 2009 Jan;9(1):55-62. | |||||
| REF 71 | The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors. Bioorg Med Chem Lett. 2010 Sep 15;20(18):5502-5. | |||||
| REF 72 | Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase. J Med Chem. 2006 Mar 23;49(6):1867-73. | |||||
| REF 73 | In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. Bioorg Med Chem. 2010 Mar 15;18(6):2204-2218. | |||||
| REF 74 | Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell Signal. 1998 Jun;10(6):427-40. | |||||
| REF 75 | First dual M3 antagonists-PDE4 inhibitors: synthesis and SAR of 4,6-diaminopyrimidine derivatives. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1834-9. | |||||
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