Target Information

Target General Infomation
Target ID
T10265
Former ID
TTDR00466
Target Name
CAMP-specific 3',5'-cyclic phosphodiesterase 4B
Gene Name
PDE4B
Synonyms
DPDE4; PDE32; Type 4 cyclic adenosine monophosphate phosphodiesterase (type 4 PDE); Type 4B cAMP phosphodiesterase; PDE4B
Target Type
Clinical Trial
Disease Asthma; Chronic obstructive pulmonary disease [ICD9: 490-492, 493, 494-496; ICD10: J40-J44, J47, J45]
Atopic dermatitis [ICD9: 691.8, 692.9; ICD10: L00-L99]
Allergy [ICD9: 995.3; ICD10: T78.4]
Asthma [ICD10: J45]
Cutaneous T-cell lymphoma [ICD9: 202.1, 202.2; ICD10: C84.0, C84.1]
Chronic lymphocytic leukaemia [ICD10: C91]
Crohn's disease [ICD9: 555; ICD10: K50]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Cognitive disorders [ICD9: 290-294, 294.0, 780.09, 780.9, 780.93; ICD10: F01-F07, F04, F05, R41.3]
Glomerulonephritis [ICD9: 580-582; ICD10: N00, N01, N03, N18]
Huntington's disease [ICD9: 294.1, 333.4; ICD10: F02.2, G10]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Lung inflammation [ICD10: D86]
Mood disorder [ICD10: F30-F39]
Multiple scierosis [ICD9: 340; ICD10: G35]
Psoriasis [ICD9: 696; ICD10: L40]
Peripheral vascular disease [ICD9: 443.9; ICD10: I73.9]
Parkinson's disease [ICD9: 332; ICD10: G20]
Rhinitis [ICD9: 472.0, 477; ICD10: J00, J30, J31.0]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Respiratory tract inflammation [ICD10: J00-J99]
Xerophthalmia [ICD10: E50.6-E50.7]
Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
BioChemical Class
Phosphoric diester hydrolases
Target Validation
T10265
UniProt ID
Q07343
EC Number
EC 3.1.4.17
Sequence
MKKSRSVMTVMADDNVKDYFECSLSKSYSSSSNTLGIDLWRGRRCCSGNLQLPPLSQRQS
ERARTPEGDGISRPTTLPLTTLPSIAITTVSQECFDVENGPSPGRSPLDPQASSSAGLVL
HATFPGHSQRRESFLYRSDSDYDLSPKAMSRNSSLPSEQHGDDLIVTPFAQVLASLRSVR
NNFTILTNLHGTSNKRSPAASQPPVSRVNPQEESYQKLAMETLEELDWCLDQLETIQTYR
SVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLDKQNDVEIPSPTQKDREKKK
KQQLMTQISGVKKLMHSSSLNNTSISRFGVNTENEDHLAKELEDLNKWGLNIFNVAGYSH
NRPLTCIMYAIFQERDLLKTFRISSDTFITYMMTLEDHYHSDVAYHNSLHAADVAQSTHV
LLSTPALDAVFTDLEILAAIFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHL
AVGFKLLQEEHCDIFMNLTKKQRQTLRKMVIDMVLATDMSKHMSLLADLKTMVETKKVTS
SGVLLLDNYTDRIQVLRNMVHCADLSNPTKSLELYRQWTDRIMEEFFQQGDKERERGMEI
SPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVQPDAQDILDTLEDNRNWYQSMIPQSP
SPPLDEQNRDCQGLMEKFQFELTLDEEDSEGPEKEGEGHSYFSSTKTLCVIDPENRDSLG
ETDIDIATEDKSPVDT
Drugs and Mode of Action
Drug(s) DENBUFYLLINE Drug Info Phase 3 Cognitive disorders [1]
SOTB07 Drug Info Phase 3 Asthma [2]
AN-2898 Drug Info Phase 2 Atopic dermatitis [3]
AWD-12-281 Drug Info Phase 2 Rhinitis [4]
CC-1088 Drug Info Phase 2 Crohn's disease [5]
GPD-1116 Drug Info Phase 2 Asthma [6]
HT-0712 Drug Info Phase 2 Cognitive disorders [7]
LIRIMILAST Drug Info Phase 2 Chronic obstructive pulmonary disease [8]
MK-0873 Drug Info Phase 2 Psoriasis [9]
Oglemilast Drug Info Phase 2 Asthma [10]
OX-914 Drug Info Phase 2 Asthma [11]
Piclamilast Drug Info Phase 2 Rheumatoid arthritis [12]
Revamilast Drug Info Phase 2 Asthma [13]
ROLIPRAM Drug Info Phase 2 Discovery agent [14], [15]
TA-7906 Drug Info Phase 2 Atopic dermatitis [16]
TOFIMILAST Drug Info Phase 2 Chronic obstructive pulmonary disease [17]
AVE-8112 Drug Info Phase 1 Parkinson's disease [18]
GSK-356278 Drug Info Phase 1 Huntington's disease [19]
MEM-1414 Drug Info Phase 1 Mood disorder [20]
Ronomilast Drug Info Phase 1 Chronic obstructive pulmonary disease [21]
CDP840 Drug Info Discontinued in Phase 2 Chronic obstructive pulmonary disease [22]
CI-1018 Drug Info Discontinued in Phase 2 Asthma [23]
Daxalipram Drug Info Discontinued in Phase 2 Multiple scierosis [24]
Filaminast Drug Info Discontinued in Phase 2 Chronic obstructive pulmonary disease [25]
KW-4490 Drug Info Discontinued in Phase 2 Asthma [26]
LAS-37779 Drug Info Discontinued in Phase 2 Psoriasis [27]
V-11294A Drug Info Discontinued in Phase 2 Asthma [28]
D-4418 Drug Info Discontinued in Phase 1 Cutaneous T-cell lymphoma [29]
SCH-351591 Drug Info Discontinued in Phase 1 Chronic obstructive pulmonary disease [30]
YM-976 Drug Info Discontinued in Phase 1 Asthma [31], [32]
D-22888 Drug Info Terminated Allergy [33]
GW-3600 Drug Info Terminated Asthma [34]
NIK-616 Drug Info Terminated Asthma; Chronic obstructive pulmonary disease [35]
TJN-598 Drug Info Terminated Glomerulonephritis [36]
Torbafylline Drug Info Terminated Peripheral vascular disease [37]
Inhibitor (R)-Mesopram Drug Info [38]
(R)-Rolipram Drug Info [39]
(S)-Rolipram Drug Info [39]
3-(2-Bromophenyl)-2-thioxo-(1H )-quinazolin-4-one Drug Info [40]
3-Isobutyl-1-methyl-3,9-dihydro-purine-2,6-dione Drug Info [41]
8-(3-Nitro-phenyl)-6-phenyl-[1,7]naphthyridine Drug Info [42]
8-Bromo-Adenosine-5'-Monophosphate Drug Info [43]
AN-2898 Drug Info [44]
ASP-3258 Drug Info [45]
AVE-8112 Drug Info [46]
AWD-12-281 Drug Info [47]
Benzyl-(2-imidazol-1-yl-quinazolin-4-yl)-amine Drug Info [48]
Benzyl-(2-phenyl-quinazolin-4-yl)-amine Drug Info [48]
Benzyl-(2-pyridin-3-yl-quinazolin-4-yl)-amine Drug Info [48]
Benzyl-(2-pyridin-4-yl-quinazolin-4-yl)-amine Drug Info [48]
Benzyl-(2-thiophen-2-yl-quinazolin-4-yl)-amine Drug Info [48]
CC-1088 Drug Info [49]
CD-160130 Drug Info [45]
CDP840 Drug Info [50]
CHF-5480 Drug Info [45]
CI-1018 Drug Info [51]
CI-1044 Drug Info [52]
D-4418 Drug Info [53]
Daxalipram Drug Info [54]
DENBUFYLLINE Drug Info [55]
Filaminast Drug Info [38]
GPD-1116 Drug Info [6]
GSK-356278 Drug Info [56]
GW-3600 Drug Info [57]
HT-0712 Drug Info [45]
KF-66490 Drug Info [58]
KURAIDIN Drug Info [59]
KURARINOL Drug Info [59]
KW-4490 Drug Info [60]
L-454560 Drug Info [61]
L-869298 Drug Info [62]
LAS-37779 Drug Info [63]
LIRIMILAST Drug Info [64]
MEM-1414 Drug Info [65]
MK-0873 Drug Info [66]
NIK-616 Drug Info [67]
NITRAQUAZONE Drug Info [68]
OCID-2987 Drug Info [45]
Oglemilast Drug Info [69]
OX-914 Drug Info [70]
PDE4 inhibitors Drug Info [45]
PDE4 inhibitors Drug Info [45]
Piclamilast Drug Info [71]
Revamilast Drug Info [72]
ROLIPRAM Drug Info [73]
Ronomilast Drug Info [74]
RS-14491 Drug Info [73]
RS-25344 Drug Info [75]
S,S-(2-Hydroxyethyl)Thiocysteine Drug Info [38]
SCH-351591 Drug Info [76]
SOPHOFLAVESCENOL Drug Info [59]
SOTB07 Drug Info [45]
TA-7906 Drug Info [77]
TAS-203 Drug Info [45]
TJN-598 Drug Info [36]
TOFIMILAST Drug Info [64]
UCB-101333-3 Drug Info [78]
V-11294A Drug Info [79]
YM-976 Drug Info [64]
Modulator AL-59640 Drug Info [45]
CH-3697 Drug Info [45]
D-22888 Drug Info [80]
Torbafylline Drug Info [37]
ZL-N-91 Drug Info [45]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Purine metabolism
cAMP signaling pathway
Morphine addiction
NetPath Pathway IL5 Signaling Pathway
IL2 Signaling Pathway
Reactome DARPP-32 events
G alpha (s) signalling events
WikiPathways G Protein Signaling Pathways
Myometrial Relaxation and Contraction Pathways
Nuclear Receptors Meta-Pathway
Opioid Signalling
References
REF 1Denbufylline in dementia: a double-blind controlled study. Dement Geriatr Cogn Disord. 1999 Nov-Dec;10(6):505-10.
REF 2ClinicalTrials.gov (NCT01907763) Study Phase III Study to Assess the Efficacy and Safety of SOTB07 in Asthma Patients. U.S. National Institutes of Health.
REF 3ClinicalTrials.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 4ClinicalTrials.gov (NCT00354510) Topical GW842470X In Adults Patients With Moderate Atopic Dermatitis. U.S. National Institutes of Health.
REF 5ClinicalTrials.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 6Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L196-204. Epub 2007 Nov 9.
REF 7Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018324)
REF 8A novel phosphodiesterase 4 inhibitor template. Expert Opinion on Therapeutic Patents,2003, 13(6), 929-933.
REF 9ClinicalTrials.gov (NCT00132730) An Investigational Drug Study In Patients With COPD (Chronic Obstructive Pulmonary Disease) (MK-0873-005). U.S. National Institutes of Health.
REF 10ClinicalTrials.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 11ClinicalTrials.gov (NCT00758446) Efficacy and Safety Study of BLX-028914 in Subjects With Allergic Rhinitis. U.S. National Institutes of Health.
REF 12Effect 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 13ClinicalTrials.gov (NCT01436890) A Clinical Trial to Study the Effects of Revamilast in Patients With Chronic Persistent Asthma. U.S. National Institutes of Health.
REF 14ClinicalTrials.gov (NCT00011375) Rolipram to Treat Multiple Sclerosis. U.S. National Institutes of Health.
REF 15(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: 5260).
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024588)
REF 17ClinicalTrials.gov (NCT00150397) A Study of the Safety and Efficacy of Tofimilast in Adult Asthmatics. U.S. National Institutes of Health.
REF 18ClinicalTrials.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 19ClinicalTrials.gov (NCT01031186) First Time in Human Study. U.S. National Institutes of Health.
REF 20The Quest for Human Longevity, Lewis D. Solo. Page(145).
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013990)
REF 22Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003087)
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010034)
REF 24Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015672)
REF 25Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003918)
REF 26Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017153)
REF 27Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022894)
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012597)
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007757)
REF 30Trusted, 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(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 32Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010783)
REF 33Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007179)
REF 34Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006447)
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020194)
REF 36Effects 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 37Phosphodiesterase (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 38How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 39PDE4 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. Epub 2009 Mar 20.
REF 40Eur J Med Chem. 2008 Jul;43(7):1349-59. Epub 2007 Dec 21.CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example.
REF 41J Med Chem. 1985 May;28(5):537-45.A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity.
REF 42J Med Chem. 2000 Feb 24;43(4):675-82.Palladium-catalyzed cross-coupling reactions for the synthesis of 6, 8-disubstituted 1,7-naphthyridines: a novel class of potent and selective phosphodiesterase type 4D inhibitors.
REF 43DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-4. Nucleic Acids Res. 2011 January
REF 44An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen. 2013 Jun;54(5):338-46.
REF 45(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: 1301).
REF 46Therapy for Parkinson's Disease: What is in the Pipeline?. Neurotherapeutics. 2014 January; 11(1): 24-33.
REF 47The 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 48J Med Chem. 1995 Sep 1;38(18):3547-57.Discovery of potent cyclic GMP phosphodiesterase inhibitors. 2-Pyridyl- and 2-imidazolylquinazolines possessing cyclic GMP phosphodiesterase and thromboxane synthesis inhibitory activities.
REF 49Bioorg Med Chem Lett. 1998 Oct 6;8(19):2669-74.Thalidomide analogs and PDE4 inhibition.
REF 50Bioorg Med Chem Lett. 2005 Dec 1;15(23):5241-6. Epub 2005 Sep 15.Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: structure-activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor.
REF 51Bioorg Med Chem Lett. 2004 Jun 21;14(12):3303-6.New substituted triaza-benzo[cd]azulen-9-ones as promising phosphodiesterase-4 inhibitors.
REF 52J Med Chem. 2000 Dec 14;43(25):4850-67.Synthesis, structure-activity relationships, and pharmacological profile of 9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6, 7,1-hi]indoles: discoveryof potent, selective phosphodiesterase type 4 inhibitors.
REF 53Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking. Br J Pharmacol. 2008 Oct;155(3):288-90.
REF 54Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice. Front Neurosci. 2014 May 27;8:129.
REF 55J Med Chem. 2002 May 23;45(11):2342-5.Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers.
REF 56GSK356278, 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 57Dual 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 58Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models. Int Immunopharmacol. 2009 Jan;9(1):55-62.
REF 59Bioorg Med Chem Lett. 2002 Sep 2;12(17):2313-6.A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5.
REF 60Pharmacokinetics 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 61Bioorg Med Chem Lett. 2010 Sep 15;20(18):5502-5. Epub 2010 Jul 21.The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors.
REF 62J Med Chem. 2006 Mar 23;49(6):1867-73.Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase.
REF 63Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022894)
REF 64Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
REF 65The 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 66MK-0873, a PDE4 inhibitor, does not influence the pharmacokinetics of theophylline in healthy male volunteers. Pulm Pharmacol Ther. 2008;21(3):573-7.
REF 67Preclinical trials in Chronic obstructive pulmonary disease in Japan (PO). 2004
REF 68Bioorg Med Chem Lett. 2000 Dec 4;10(23):2661-4.Synthesis and biological evaluation of 2,5-dihydropyrazol.
REF 69Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking?. Br J Pharmacol. 2008 October; 155(3): 288-290.
REF 70Orexo announces Phase IIa data on OX914 in rhinitis. Orexo. 24th March, 2009.
REF 71Effects of piclamilast, a selective phosphodiesterase-4 inhibitor, on oxidative burst of sputum cells from mild asthmatics and stable <span class="caps">COPD</span> patients. Lung. 2004;182(6):369-77.
REF 72WO patent application no. 2012,1109,46, Pharmaceutical composition comprising the pde4 enzyme inhibitor revamilast and a disease modifying agent, preferably methotrexate .
REF 73J Med Chem. 1997 May 9;40(10):1417-21.Novel heterocyclic-fused pyridazinones as potent and selective phosphodiesterase IV inhibitors.
REF 74Clinical pipeline report, company report or official report of Avarx.
REF 75Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell Signal. 1998 Jun;10(6):427-40.
REF 76Bioorg Med Chem Lett. 2002 Jun 17;12(12):1621-3.Synthesis and profile of SCH351591, a novel PDE4 inhibitor.
REF 77Potential 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 78Bioorg Med Chem Lett. 2006 Apr 1;16(7):1834-9. Epub 2006 Jan 24.First dual M3 antagonists-PDE4 inhibitors: synthesis and SAR of 4,6-diaminopyrimidine derivatives.
REF 79Pharmacokinetic 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 80Effects 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.

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