Target Information

Target General Infomation
Target ID
T88975
Former ID
TTDS00390
Target Name
CGMP-inhibited 3',5'-cyclic phosphodiesterase A
Gene Name
PDE3A
Synonyms
CGI-PDE A; Cyclic GMP inhibited phosphodiesterase A; Phosphodiesterase 3A; PDE3A
Target Type
Successful
Disease Asthma [ICD10: J45]
Bronchial asthma [ICD9: 493; ICD10: J45]
Cardiovascular disorder [ICD10: I00-I99]
Cardiac failure [ICD10: I50]
Heart failure [ICD9: 428; ICD10: I50]
Thrombocythemia [ICD9: 289.9; ICD10: D75.8]
Function
Cyclic nucleotide phosphodiesterase with a dual- specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
BioChemical Class
Phosphoric diester hydrolases
Target Validation
T88975
UniProt ID
Q14432
EC Number
EC 3.1.4.17
Sequence
MAVPGDAARVRDKPVHSGVSQAPTAGRDCHHRADPASPRDSGCRGCWGDLVLQPLRSSRK
LSSALCAGSLSFLLALLVRLVRGEVGCDLEQCKEAAAAEEEEAAPGAEGGVFPGPRGGAP
GGGARLSPWLQPSALLFSLLCAFFWMGLYLLRAGVRLPLAVALLAACCGGEALVQIGLGV
GEDHLLSLPAAGVVLSCLAAATWLVLRLRLGVLMIALTSAVRTVSLISLERFKVAWRPYL
AYLAGVLGILLARYVEQILPQSAEAAPREHLGSQLIAGTKEDIPVFKRRRRSSSVVSAEM
SGCSSKSHRRTSLPCIPREQLMGHSEWDHKRGPRGSQSSGTSITVDIAVMGEAHGLITDL
LADPSLPPNVCTSLRAVSNLLSTQLTFQAIHKPRVNPVTSLSENYTCSDSEESSEKDKLA
IPKRLRRSLPPGLLRRVSSTWTTTTSATGLPTLEPAPVRRDRSTSIKLQEAPSSSPDSWN
NPVMMTLTKSRSFTSSYAISAANHVKAKKQSRPGALAKISPLSSPCSSPLQGTPASSLVS
KISAVQFPESADTTAKQSLGSHRALTYTQSAPDLSPQILTPPVICSSCGRPYSQGNPADE
PLERSGVATRTPSRTDDTAQVTSDYETNNNSDSSDIVQNEDETECLREPLRKASACSTYA
PETMMFLDKPILAPEPLVMDNLDSIMEQLNTWNFPIFDLVENIGRKCGRILSQVSYRLFE
DMGLFEAFKIPIREFMNYFHALEIGYRDIPYHNRIHATDVLHAVWYLTTQPIPGLSTVIN
DHGSTSDSDSDSGFTHGHMGYVFSKTYNVTDDKYGCLSGNIPALELMALYVAAAMHDYDH
PGRTNAFLVATSAPQAVLYNDRSVLENHHAAAAWNLFMSRPEYNFLINLDHVEFKHFRFL
VIEAILATDLKKHFDFVAKFNGKVNDDVGIDWTNENDRLLVCQMCIKLADINGPAKCKEL
HLQWTDGIVNEFYEQGDEEASLGLPISPFMDRSAPQLANLQESFISHIVGPLCNSYDSAG
LMPGKWVEDSDESGDTDDPEEEEEEAPAPNEEETCENNESPKKKTFKRRKIYCQITQHLL
QNHKMWKKVIEEEQRLAGIENQSLDQTPQSHSSEQIQAIKEEEEEKGKPRGEEIPTQKPD
Q
Drugs and Mode of Action
Drug(s) Aminophylline Drug Info Approved Bronchial asthma [1]
Anagrelide Drug Info Approved Thrombocythemia [2], [3]
VESNARINONE Drug Info Approved Cardiac failure [4]
Aminophylline Drug Info Phase 2 Asthma [5]
BEMORADAN Drug Info Phase 2 Heart failure [6]
CI-930 Drug Info Discontinued in Phase 2 Discovery agent [7]
EMD-53998 Drug Info Discontinued in Phase 1 Cardiovascular disorder [8]
BMY-20844 Drug Info Terminated Discovery agent [9]
IMAZODAN Drug Info Terminated Discovery agent [10]
LAS-31180 Drug Info Terminated Heart failure [11]
Inhibitor 1,3,9,9a-Tetrahydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
1,3-Dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
1,3-Dihydro-naphtho[2,3-d]imidazol-2-one Drug Info [12]
1,5-Dihydro-imidazo[2,1-b]quinazolin-2-one Drug Info [13]
2-Morpholin-4-yl-8-phenylethynyl-chromen-4-one Drug Info [14]
2-morpholino-7-(2-phenylethynyl)-4H-chromen-4-one Drug Info [14]
2-morpholino-7-phenyl-4H-chromen-4-one Drug Info [14]
3-Isobutyl-1-methyl-3,9-dihydro-purine-2,6-dione Drug Info [15]
5-Methyl-1,3-dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
6-(2-Imidazol-1-yl-vinyl)-1H-quinolin-2-one Drug Info [16]
6-Imidazol-1-yl-3,4-dihydro-1H-quinolin-2-one Drug Info [16]
6-Pyridin-3-yl-3,4-dihydro-1H-quinolin-2-one Drug Info [16]
7-Chloro-1,3-dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
7-Ethoxy-1,3-dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
7-Fluoro-1,3-dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
7-Iodo-1,5-dihydro-imidazo[2,1-b]quinazolin-2-one Drug Info [13]
7-Methyl-1,3-dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
8-Chloro-1,3-dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
8-Methyl-1,3-dihydro-imidazo[4,5-b]quinolin-2-one Drug Info [12]
8-methyl-2-morpholino-7-phenoxy-4H-chromen-4-one Drug Info [14]
8-methyl-2-morpholino-7-phenyl-4H-chromen-4-one Drug Info [14]
Aminophylline Drug Info [17], [18]
Anagrelide Drug Info [19]
BEMORADAN Drug Info [4]
BENZOYLENUREA Drug Info [20]
BMY-20844 Drug Info [21]
CI-930 Drug Info [22]
EMD-53998 Drug Info [4]
FENOXIMONE Drug Info [23]
IMAZODAN Drug Info [16]
KURAIDIN Drug Info [24]
KURARINOL Drug Info [24]
OPC-13013 Drug Info [15]
SOPHOFLAVESCENOL Drug Info [24]
TETRAHYDROBENXIMIDAZOLE Drug Info [22]
VESNARINONE Drug Info [25]
Modulator LAS-31180 Drug Info [11]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Purine metabolism
cGMP-PKG signaling pathway
cAMP signaling pathway
Morphine addiction
Reactome cGMP effects
G alpha (s) signalling events
WikiPathways miR-targeted genes in muscle cell - TarBase
miR-targeted genes in lymphocytes - TarBase
References
REF 1FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 081142.
REF 2Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 3(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: 7114).
REF 4Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 5Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63.
REF 6Evaluation of the excretion, and metabolism of the cardiotonic agent bemoradan in male rats and female beagle dogs. Eur J Drug Metab Pharmacokinet. 2001 Oct-Dec;26(4):263-71.
REF 7Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000144)
REF 8Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000367)
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000364)
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000379)
REF 11Pharmacological profile of LAS 31180, a new inotropic/vasodilator quinolone derivative. Arzneimittelforschung. 2000 Nov;50(11):980-6.
REF 12J Med Chem. 1991 Sep;34(9):2906-16.1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-ones--inhibitors of blood platelet cAMP phosphodiesterase and induced aggregation.
REF 13J Med Chem. 1988 Nov;31(11):2136-45.Inhibitors of cyclic AMP phosphodiesterase. 3. Synthesis and biological evaluation of pyrido and imidazolyl analogues of 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline.
REF 14Bioorg Med Chem Lett. 2006 Feb 15;16(4):969-73. Epub 2005 Nov 15.Analysis of anti-PDE3 activity of 2-morpholinochromone derivatives reveals multiple mechanisms of anti-platelet activity.
REF 15J 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 16J Med Chem. 1992 Feb 21;35(4):620-8.3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase.
REF 17Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Acta Anaesthesiol Scand. 2002 Mar;46(3):297-302.
REF 18Topical fat reduction from the waist. Diabetes Obes Metab. 2007 May;9(3):300-3.
REF 19Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45.
REF 20Eur 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 21J Med Chem. 1992 Jul 10;35(14):2688-96.Inhibitors of blood platelet cAMP phosphodiesterase. 3. 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives with enhanced aqueous solubility.
REF 22J Med Chem. 1989 Feb;32(2):342-50.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.
REF 23J Med Chem. 1987 Feb;30(2):303-18.Inhibitors of cyclic AMP phosphodiesterase. 2. Structural variations of N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro- 2-oxoimidazo[2,1-b]quinazolin-7-yl)-oxy]butyramide (RS-82856).
REF 24Bioorg Med Chem Lett. 2002 Sep 2;12(17):2313-6.A prenylated flavonol, sophoflavescenol: a potent and selective inhibitor of cGMP phosphodiesterase 5.
REF 25Bioorg Med Chem. 2010 Jan 15;18(2):855-62. Epub 2009 Nov 26.Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors.

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