Target Information
Target General Information | Top | |||||
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Target ID |
T61744
(Former ID: TTDS00280)
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Target Name |
Phosphodiesterase 4A (PDE4A)
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Synonyms |
cAMP-specific 3',5'-cyclic phosphodiesterase 4A; Type 4A cAMP phosphodiesterase; PDE46; DPDE2
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Gene Name |
PDE4A
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Asthma [ICD-11: CA23] | |||||
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 |
MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ
PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T95GWW |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | Dyphylline | Drug Info | Approved | Acute bronchial asthma | [2], [3], [4] | |
2 | Enprofylline | Drug Info | Approved | Asthma | [5] | |
Clinical Trial Drug(s) | [+] 20 Clinical Trial Drugs | + | ||||
1 | DENBUFYLLINE | Drug Info | Phase 3 | Cognitive impairment | [6] | |
2 | SOTB07 | Drug Info | Phase 3 | Asthma | [7] | |
3 | AN-2898 | Drug Info | Phase 2 | Atopic dermatitis | [8] | |
4 | AWD-12-281 | Drug Info | Phase 2 | Rhinitis | [9] | |
5 | CC-1088 | Drug Info | Phase 2 | Crohn disease | [10] | |
6 | GPD-1116 | Drug Info | Phase 2 | Asthma | [11] | |
7 | HT-0712 | Drug Info | Phase 2 | Cognitive impairment | [12] | |
8 | LIRIMILAST | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [13] | |
9 | MK-0873 | Drug Info | Phase 2 | Psoriasis vulgaris | [14] | |
10 | Oglemilast | Drug Info | Phase 2 | Asthma | [15] | |
11 | OX-914 | Drug Info | Phase 2 | Asthma | [16] | |
12 | Piclamilast | Drug Info | Phase 2 | Rheumatoid arthritis | [17] | |
13 | Revamilast | Drug Info | Phase 2 | Asthma | [18] | |
14 | TA-7906 | Drug Info | Phase 2 | Atopic dermatitis | [19] | |
15 | TOFIMILAST | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [20] | |
16 | Tofisopam | Drug Info | Phase 2 | Irritable bowel syndrome | [21] | |
17 | AVE-8112 | Drug Info | Phase 1 | Parkinson disease | [22] | |
18 | GSK-356278 | Drug Info | Phase 1 | Huntington disease | [23] | |
19 | MEM-1414 | Drug Info | Phase 1 | Mood disorder | [24] | |
20 | Ronomilast | Drug Info | Phase 1 | Chronic obstructive pulmonary disease | [25] | |
Discontinued Drug(s) | [+] 16 Discontinued Drugs | + | ||||
1 | Cilomilast | Drug Info | Discontinued in Phase 3 | Chronic obstructive pulmonary disease | [26], [27] | |
2 | CDP840 | Drug Info | Discontinued in Phase 2 | Chronic obstructive pulmonary disease | [28] | |
3 | CI-1018 | Drug Info | Discontinued in Phase 2 | Asthma | [29] | |
4 | Daxalipram | Drug Info | Discontinued in Phase 2 | Multiple sclerosis | [30] | |
5 | GSK256066 | Drug Info | Discontinued in Phase 2 | Asthma | [31] | |
6 | KW-4490 | Drug Info | Discontinued in Phase 2 | Asthma | [32] | |
7 | LAS-37779 | Drug Info | Discontinued in Phase 2 | Psoriasis vulgaris | [33] | |
8 | V-11294A | Drug Info | Discontinued in Phase 2 | Asthma | [34] | |
9 | D-4418 | Drug Info | Discontinued in Phase 1 | Cutaneous T-cell lymphoma | [35] | |
10 | SCH-351591 | Drug Info | Discontinued in Phase 1 | Chronic obstructive pulmonary disease | [36] | |
11 | YM-976 | Drug Info | Discontinued in Phase 1 | Asthma | [37], [38] | |
12 | D-22888 | Drug Info | Terminated | Allergy | [39] | |
13 | GW-3600 | Drug Info | Terminated | Asthma | [40] | |
14 | NIK-616 | Drug Info | Terminated | Chronic obstructive pulmonary disease | [41] | |
15 | TJN-598 | Drug Info | Terminated | Glomerulonephritis | [42] | |
16 | Torbafylline | Drug Info | Terminated | Peripheral vascular disease | [43] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 80 Inhibitor drugs | + | ||||
1 | Dyphylline | Drug Info | [1] | |||
2 | Enprofylline | Drug Info | [5] | |||
3 | DENBUFYLLINE | Drug Info | [44] | |||
4 | SOTB07 | Drug Info | [45] | |||
5 | AN-2898 | Drug Info | [46] | |||
6 | AWD-12-281 | Drug Info | [47] | |||
7 | CC-1088 | Drug Info | [48] | |||
8 | GPD-1116 | Drug Info | [11] | |||
9 | HT-0712 | Drug Info | [45] | |||
10 | LIRIMILAST | Drug Info | [49] | |||
11 | MK-0873 | Drug Info | [50] | |||
12 | Oglemilast | Drug Info | [49] | |||
13 | OX-914 | Drug Info | [51] | |||
14 | Piclamilast | Drug Info | [52] | |||
15 | Revamilast | Drug Info | [53] | |||
16 | TA-7906 | Drug Info | [54] | |||
17 | TOFIMILAST | Drug Info | [55] | |||
18 | Tofisopam | Drug Info | [56] | |||
19 | AVE-8112 | Drug Info | [57] | |||
20 | GSK-356278 | Drug Info | [58] | |||
21 | MEM-1414 | Drug Info | [59] | |||
22 | Ronomilast | Drug Info | [60] | |||
23 | Cilomilast | Drug Info | [27] | |||
24 | CDP840 | Drug Info | [61] | |||
25 | CI-1018 | Drug Info | [62] | |||
26 | Daxalipram | Drug Info | [63] | |||
27 | GSK256066 | Drug Info | [64] | |||
28 | KW-4490 | Drug Info | [65] | |||
29 | LAS-37779 | Drug Info | [66] | |||
30 | V-11294A | Drug Info | [67] | |||
31 | D-4418 | Drug Info | [68] | |||
32 | SCH-351591 | Drug Info | [69] | |||
33 | YM-976 | Drug Info | [70] | |||
34 | D-22888 | Drug Info | [71] | |||
35 | GW-3600 | Drug Info | [72] | |||
36 | NIK-616 | Drug Info | [73] | |||
37 | TJN-598 | Drug Info | [42] | |||
38 | Torbafylline | Drug Info | [43] | |||
39 | (2,5-Diphenyl-furan-3-yl)-phenyl-methanone | Drug Info | [74] | |||
40 | (R)-Rolipram | Drug Info | [75] | |||
41 | (S)-Rolipram | Drug Info | [75] | |||
42 | 1-Butyl-3-methyl-3,7-dihydro-purine-2,6-dione | Drug Info | [76] | |||
43 | 1-Methyl-3-propyl-3,7-dihydro-purine-2,6-dione | Drug Info | [76] | |||
44 | 2,5-Bis-(3,4-dimethoxy-phenyl)-furan | Drug Info | [74] | |||
45 | 2,5-Bis-(3-cyclopentyloxy-4-methoxy-phenyl)-furan | Drug Info | [74] | |||
46 | 4-(2,5-Diphenyl-furan-3-yl)-morpholine | Drug Info | [74] | |||
47 | 6-Azido-8-(3-iodo-phenyl)-quinoline | Drug Info | [77] | |||
48 | 6-Imidazol-1-ylmethyl-8-phenyl-quinoline | Drug Info | [77] | |||
49 | 8-(3-Azido-phenyl)-6-iodo-quinoline | Drug Info | [77] | |||
50 | 8-(3-Azido-phenyl)-6-pyridin-4-ylmethyl-quinoline | Drug Info | [77] | |||
51 | 8-(3-Nitro-phenyl)-6-phenyl-[1,7]naphthyridine | Drug Info | [78] | |||
52 | 8-(3-Nitro-phenyl)-6-pyridin-4-ylmethyl-quinoline | Drug Info | [77] | |||
53 | AL-59640 | Drug Info | [45] | |||
54 | ASP-3258 | Drug Info | [45] | |||
55 | Benzyl-(2-imidazol-1-yl-quinazolin-4-yl)-amine | Drug Info | [79] | |||
56 | Benzyl-(2-phenyl-quinazolin-4-yl)-amine | Drug Info | [79] | |||
57 | Benzyl-(2-pyridin-3-yl-quinazolin-4-yl)-amine | Drug Info | [79] | |||
58 | Benzyl-(2-pyridin-4-yl-quinazolin-4-yl)-amine | Drug Info | [79] | |||
59 | Benzyl-(2-thiophen-2-yl-quinazolin-4-yl)-amine | Drug Info | [79] | |||
60 | CD-160130 | Drug Info | [45] | |||
61 | CH-3697 | Drug Info | [45] | |||
62 | CHF-5480 | Drug Info | [45] | |||
63 | CI-1044 | Drug Info | [80] | |||
64 | isobutylmethylxanthine | Drug Info | [81] | |||
65 | KF-66490 | Drug Info | [82] | |||
66 | KURAIDIN | Drug Info | [83] | |||
67 | KURARINOL | Drug Info | [83] | |||
68 | L-454560 | Drug Info | [84] | |||
69 | L-791943 | Drug Info | [85] | |||
70 | L-869298 | Drug Info | [86] | |||
71 | NIS-62949 | Drug Info | [87] | |||
72 | NITRAQUAZONE | Drug Info | [88] | |||
73 | OCID-2987 | Drug Info | [45] | |||
74 | ROLIPRAM | Drug Info | [89] | |||
75 | RS-14491 | Drug Info | [90] | |||
76 | RS-25344 | Drug Info | [91] | |||
77 | SOPHOFLAVESCENOL | Drug Info | [83] | |||
78 | TAS-203 | Drug Info | [45] | |||
79 | UCB-101333-3 | Drug Info | [92] | |||
80 | ZL-N-91 | Drug Info | [45] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(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 | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | Purine metabolism | |||||
2 | cAMP signaling pathway | |||||
3 | Morphine addiction | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | DARPP-32 events | |||||
2 | G alpha (s) signalling events | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | G Protein Signaling Pathways |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94. | |||||
REF 2 | 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: 7070). | |||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 4 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 007794. | |||||
REF 5 | Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium. Am J Obstet Gynecol. 1987 Apr;156(4):958-62. | |||||
REF 6 | Denbufylline in dementia: a double-blind controlled study. Dement Geriatr Cogn Disord. 1999 Nov-Dec;10(6):505-10. | |||||
REF 7 | 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 8 | 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 9 | ClinicalTrials.gov (NCT00354510) Topical GW842470X In Adults Patients With Moderate Atopic Dermatitis. U.S. National Institutes of Health. | |||||
REF 10 | 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 11 | 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 12 | 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 13 | A novel phosphodiesterase 4 inhibitor template. Expert Opinion on Therapeutic Patents,2003, 13(6), 929-933. | |||||
REF 14 | 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 15 | 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 16 | ClinicalTrials.gov (NCT00758446) Efficacy and Safety Study of BLX-028914 in Subjects With Allergic Rhinitis. U.S. National Institutes of Health. | |||||
REF 17 | 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 18 | 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 19 | 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 20 | ClinicalTrials.gov (NCT00150397) A Study of the Safety and Efficacy of Tofimilast in Adult Asthmatics. U.S. National Institutes of Health. | |||||
REF 21 | ClinicalTrials.gov (NCT00486876) A Study of 3 Doses of Dextofisopam in Females With Irritable Bowel Syndrome. U.S. National Institutes of Health. | |||||
REF 22 | 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 23 | ClinicalTrials.gov (NCT01031186) First Time in Human Study. U.S. National Institutes of Health. | |||||
REF 24 | The Quest for Human Longevity, Lewis D. Solo. Page(145). | |||||
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 800013990) | |||||
REF 26 | 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: 7407). | |||||
REF 27 | Emerging drugs for asthma. Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53. | |||||
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 800003087) | |||||
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 800010034) | |||||
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 800015672) | |||||
REF 31 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024245) | |||||
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 800017153) | |||||
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 800022894) | |||||
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 800012597) | |||||
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 800007757) | |||||
REF 36 | 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 37 | 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 38 | 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 39 | 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 40 | 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 41 | 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 42 | 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 43 | 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 44 | Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. J Med Chem. 2002 May 23;45(11):2342-5. | |||||
REF 45 | 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: 1300). | |||||
REF 46 | An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen. 2013 Jun;54(5):338-46. | |||||
REF 47 | 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 48 | Thalidomide analogs and PDE4 inhibition. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2669-74. | |||||
REF 49 | 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 50 | 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 51 | Orexo announces Phase IIa data on OX914 in rhinitis. Orexo. 24th March, 2009. | |||||
REF 52 | 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 53 | WO patent application no. 2012,1109,46, Pharmaceutical composition comprising the pde4 enzyme inhibitor revamilast and a disease modifying agent, preferably methotrexate . | |||||
REF 54 | 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 55 | GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54. | |||||
REF 56 | The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. | |||||
REF 57 | Therapy for Parkinson's Disease: What is in the Pipeline . Neurotherapeutics. 2014 January; 11(1): 24-33. | |||||
REF 58 | 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 59 | 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 60 | Clinical pipeline report, company report or official report of Avarx. | |||||
REF 61 | 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 62 | 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 63 | Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice. Front Neurosci. 2014 May 27;8:129. | |||||
REF 64 | Clinical pipeline report, company report or official report of GlaxoSmithKline (2009). | |||||
REF 65 | 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 66 | 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 67 | 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 68 | 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 69 | Synthesis and profile of SCH351591, a novel PDE4 inhibitor. Bioorg Med Chem Lett. 2002 Jun 17;12(12):1621-3. | |||||
REF 70 | Antiasthmatic effect of YM976, a novel PDE4 inhibitor, in guinea pigs. J Pharmacol Exp Ther. 2001 Apr;297(1):165-73. | |||||
REF 71 | 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 72 | 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 73 | Preclinical trials in Chronic obstructive pulmonary disease in Japan (PO). 2004 | |||||
REF 74 | Substituted furans as inhibitors of the PDE4 enzyme. Bioorg Med Chem Lett. 1999 Feb 8;9(3):323-6. | |||||
REF 75 | PDE4 inhibitors roflumilast and rolipram augment PGE2 inhibition of TGF-{beta}1-stimulated fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L959-69. | |||||
REF 76 | Effects of alkyl substitutions of xanthine skeleton on bronchodilation. J Med Chem. 1992 Oct 30;35(22):4039-44. | |||||
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