Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDS00280

Target Information
NameCAMP-specific 3',5'-cyclic phosphodiesterase 4A    
Type of targetSuccessful target    
SynonymsDPDE2    
PDE46    
Type 4A cAMP phosphodiesterase    
DiseaseChronic lymphocytic leukemia
[ICD9: 204.1   ICD10: C91.1]
[1]
Drug(s)DyphyllineApprovedAcute bronchial asthma[2]
EnprofyllineApprovedAsthma[3]
GSK256066Phase II completedCOPD & Asthma[4]
CilomilastSuspended in Phase II in GSK 2005 ReportAsthma, Chronic obstructive pulmonary disease (COPD)[5]
BioChemical ClassHydrolases acting on ester bonds    
EC NumberEC 3.1.4.17
PathwayPurine metabolism
UniProt IDP27815
PDB Structure2QYK; 3I8V; 3TVX.    
SequenceMEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
Related US Patent6,635,436
Target ValidationClick to Find Target Validation Information.    
Inhibitor (-)-ROLIPRAM[6]
(2,5-Diphenyl-furan-3-yl)-phenyl-methanone[7]
(R)-Rolipram[8]
(S)-Rolipram[8]
1-Butyl-3-methyl-3,7-dihydro-purine-2,6-dione[9]
1-Methyl-3-propyl-3,7-dihydro-purine-2,6-dione[9]
2,5-Bis- (3,4-dimethoxy-phenyl)-furan[7]
2,5-Bis- (3-cyclopentyloxy-4-methoxy-phenyl)-furan[7]
3-Isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione[10]
4- (2,5-Diphenyl-furan-3-yl)-morpholine[7]
6-Azido-8- (3-iodo-phenyl)-quinoline[11]
6-Imidazol-1-ylmethyl-8-phenyl-quinoline[11]
8- (3-Azido-phenyl)-6-iodo-quinoline[11]
8- (3-Azido-phenyl)-6-pyridin-4-ylmethyl-quinoline[11]
8- (3-Nitro-phenyl)-6-phenyl-[1,7]naphthyridine[12]
8- (3-Nitro-phenyl)-6-pyridin-4-ylmethyl-quinoline[11]
Benzyl- (2-imidazol-1-yl-quinazolin-4-yl)-amine[13]
Benzyl- (2-phenyl-quinazolin-4-yl)-amine[13]
Benzyl- (2-pyridin-3-yl-quinazolin-4-yl)-amine[13]
Benzyl- (2-pyridin-4-yl-quinazolin-4-yl)-amine[13]
Benzyl- (2-thiophen-2-yl-quinazolin-4-yl)-amine[13]
CC-1088[14]
CDP840[15]
CI-1018[16]
CI-1044[17]
Cilomilast[5]
DENBUFYLLINE[18]
Dyphylline[2]
Enprofylline[3]
GSK256066[4]
KURAIDIN[19]
KURARINOL[19]
L-454560[20]
L-791943[21]
L-869298[22]
NIS-62949[23]
NITRAQUAZONE[24]
Piclamilast[25]
RO-201724[26]
ROLIPRAM[27]
RS-14491[28]
SCH-351591[29]
SCH-365351[30]
SOPHOFLAVESCENOL[19]
UCB-101333-3[31]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Type 4 cyclic adenosine monophosphate phosphodiesterase as a therapeutic target in chronic lymphocytic leukemia. Blood. 1998 Oct 1;92(7):2484-94. To Reference
Ref 2Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94. To Reference
Ref 3Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium. Am J Obstet Gynecol. 1987 Apr;156(4):958-62. To Reference
Ref 4GSK. Product Development Pipeline. February 2009. To Reference
Ref 5Emerging drugs for asthma. Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53. To Reference
Ref 6J Med Chem. 2007 Jan 25;50(2):344-9.SAR of a series of 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridines as potent inhibitors of human eosinophil phosphodiesterase. To Reference
Ref 7Bioorg Med Chem Lett. 1999 Feb 8;9(3):323-6.Substituted furans as inhibitors of the PDE4 enzyme. To Reference
Ref 8PDE4 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. To Reference
Ref 9J Med Chem. 1992 Oct 30;35(22):4039-44.Effects of alkyl substitutions of xanthine skeleton on bronchodilation. To Reference
Ref 10J 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. To Reference
Ref 11J Med Chem. 2000 Oct 19;43(21):3820-3.Hunting the emesis and efficacy targets of PDE4 inhibitors: identification of the photoaffinity probe 8-(3-azidophenyl)-6- [(4-iodo-1H-1-imidazolyl)methyl]quinoline (APIIMQ). To Reference
Ref 12J 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. To Reference
Ref 13J 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. To Reference
Ref 14Bioorg Med Chem Lett. 1998 Oct 6;8(19):2669-74.Thalidomide analogs and PDE4 inhibition. To Reference
Ref 15Bioorg 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. To Reference
Ref 16Bioorg Med Chem Lett. 2004 Jun 21;14(12):3303-6.New substituted triaza-benzo[cd]azulen-9-ones as promising phosphodiesterase-4 inhibitors. To Reference
Ref 17J 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: discovery of potent, selective phosphodiesterase type 4 inhibitors. To Reference
Ref 18J Med Chem. 2002 May 23;45(11):2342-5.Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. To Reference
Ref 19Bioorg Med Chem Lett. 2002 Sep 2;12(17):2313-6.A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5. To Reference
Ref 20Bioorg 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. To Reference
Ref 21Bioorg Med Chem Lett. 2002 Jun 3;12(11):1457-61.Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor. To Reference
Ref 22J Med Chem. 2006 Mar 23;49(6):1867-73.Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase. To Reference
Ref 23Pharmacology of a novel, orally active PDE4 inhibitor. Pharmacology. 2009;83(5):275-86. Epub 2009 Mar 25. To Reference
Ref 24Bioorg Med Chem Lett. 2000 Dec 4;10(23):2661-4.Synthesis and biological evaluation of 2,5-dihydropyrazol. To Reference
Ref 25Beeh KM, Beier J, Lerch C, Schulz AK, Buhl R: 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. To Reference
Ref 26J Med Chem. 1991 Jan;34(1):291-8.Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones. To Reference
Ref 27Bioorg. Med. Chem. Lett. 5(17):1965-1968 (1995) To Reference
Ref 28J Med Chem. 1997 May 9;40(10):1417-21.Novel heterocyclic-fused pyridazinones as potent and selective phosphodiesterase IV inhibitors. To Reference
Ref 29Bioorg Med Chem Lett. 2002 Jun 17;12(12):1621-3.Synthesis and profile of SCH351591, a novel PDE4 inhibitor. To Reference
Ref 30Bioorg Med Chem Lett. 2002 Jun 17;12(12):1617-9.8-Methoxyquinolines as PDE4 inhibitors. To Reference
Ref 31Bioorg 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. To Reference



 

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