Target Information

Target General Information

Target ID

T33754 (Former ID: TTDS00200)

Target Name

Phosphodiesterase 3 (PDE3)

Synonyms

Phosphodiesterase III; PDE3; Cyclic GMP inhibited phosphodiesterase; Cyclic AMP phosphodiesterase III; CGI-PDE; CAMP phosphodiesterase III

Click to Show/Hide

Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 5 Target-related Diseases

Arterial occlusive disease [ICD-11: BD40]

Cardiovascular disease [ICD-11: BA00-BE2Z]

Castlemans disease [ICD-11: 4B2Y]

Cough [ICD-11: MD12]

Heart failure [ICD-11: BD10-BD1Z]

BioChemical Class

Phosphoric diester hydrolase

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 7 Approved Drugs

Cilostazol

Drug Info

Approved

Intermittent claudication

[2], [3]

Enoximone

Drug Info

Approved

Congestive heart failure

[4]

Ibudilast

Drug Info

Approved

Castleman's disease

[5]

Inamrinone Lactate

Drug Info

Approved

Congestive heart failure

[4], [6]

Milrinone

Drug Info

Approved

Congestive heart failure

[4], [7]

Olprinone

Drug Info

Approved

Heart failure

[6], [8]

Oxtriphylline

Drug Info

Approved

Cough

[9]

Clinical Trial Drug(s)

[+] 7 Clinical Trial Drugs

K-134

Drug Info

Phase 2

Arteriosclerosis

[10]

Org-30029

Drug Info

Phase 2

Heart failure

[11]

RPL-554

Drug Info

Phase 2

Allergic rhinitis

[12]

Tipelukast

Drug Info

Phase 2

Asthma

[13]

Tofisopam

Drug Info

Phase 2

Irritable bowel syndrome

[14]

349U85.HCL

Drug Info

Phase 1

Cardiovascular disease

[15], [16]

SDZ-MKS-492

Drug Info

Phase 1

Asthma

[17], [18]

Discontinued Drug(s)

[+] 13 Discontinued Drugs

NSP-805

Drug Info

Discontinued in Phase 2

Heart failure

[19]

OPC-8490

Drug Info

Discontinued in Phase 2

Cardiovascular disease

[20]

Org-9731

Drug Info

Discontinued in Phase 2

Heart failure

[21]

Pumafentrine

Drug Info

Discontinued in Phase 2

Asthma

[22]

Tolafentrine

Drug Info

Discontinued in Phase 2

Chronic obstructive pulmonary disease

[23]

NIP-520

Drug Info

Discontinued in Phase 1

Asthma

[24]

R 80122

Drug Info

Discontinued in Phase 1

Cardiovascular disease

[25]

Benafentrine dimaleate

Drug Info

Terminated

Sepsis

[26]

Org-9935

Drug Info

Terminated

Asthma

[27]

SDZ-ISQ-844

Drug Info

Terminated

Asthma

[28]

Siguazodan

Drug Info

Terminated

Allergy

[29]

UD-CG-212

Drug Info

Terminated

Heart failure

[30]

ZARDAVERINE

Drug Info

Terminated

Chronic obstructive pulmonary disease

[31]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 23 Modulator drugs

Cilostazol

Drug Info

[32]

Enoximone

Drug Info

[33]

Milrinone

Drug Info

[32]

Oxtriphylline

Drug Info

[32]

K-134

Drug Info

[35], [36]

Org-30029

Drug Info

[11], [37]

RPL-554

Drug Info

[38]

Tipelukast

Drug Info

[39]

349U85.HCL

Drug Info

[15]

SDZ-MKS-492

Drug Info

[17], [18]

NSP-805

Drug Info

[41], [41]

OPC-8490

Drug Info

[42]

Org-9731

Drug Info

[43], [44]

Pumafentrine

Drug Info

[45]

Tolafentrine

Drug Info

[46]

NIP-520

Drug Info

[47]

R 80122

Drug Info

[48], [49]

Benafentrine dimaleate

Drug Info

[50]

Org-9935

Drug Info

[51]

SDZ-ISQ-844

Drug Info

[52], [53]

Siguazodan

Drug Info

[54]

UD-CG-212

Drug Info

[55], [56]

ZARDAVERINE

Drug Info

[57]

Inhibitor

[+] 5 Inhibitor drugs

Ibudilast

Drug Info

[5]

Inamrinone Lactate

Drug Info

[1]

Olprinone

Drug Info

[34]

Tofisopam

Drug Info

[40]

Cilostamide

Drug Info

[58]

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

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8.

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: 7148).

REF 3

Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.

REF 4

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 5

Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.

REF 6

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 7

REF 8

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000438)

REF 9

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 086742.

REF 10

ClinicalTrials.gov (NCT00783081) Safety and Efficacy of K-134 for the Treatment of Intermittent Claudication. U.S. National Institutes of Health.

REF 11

Effects of the positive inotropic agent Org 30029 on developed force and aequorin light transients in intact canine ventricular myocardium. Circ Res. 1993 Mar;72(3):597-606.

REF 12

ClinicalTrials.gov (NCT02427165) Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients. U.S. National Institutes of Health.

REF 13

ClinicalTrials.gov (NCT02503657) Safety and Tolerability Study in Subjects With Idiopathic Pulmonary Fibrosis (IPF).

REF 14

ClinicalTrials.gov (NCT00486876) A Study of 3 Doses of Dextofisopam in Females With Irritable Bowel Syndrome. U.S. National Institutes of Health.

REF 15

Pharmacokinetics and pharmacodynamics of a new cardiotonic vasodilator agent, 349U85, in normal subjects. Clin Pharmacol Ther. 1994 Jan;55(1):55-63.

REF 16

Cardiovascular pharmacology of the vasodilator-cardiotonic agent, 349U85. J Cardiovasc Pharmacol. 1992 Oct;20(4):579-89.

REF 17

Effects of a cyclic nucleotide phosphodiesterase isoenzyme type III inhibitor, SDZ MKS 492 on airway responsiveness in beagles. Arerugi. 1993 Aug;42(8):920-5.

REF 18

Effects of MKS-492 on antigen-induced bronchoconstriction and allergic reaction in guinea pigs and rats. Jpn J Pharmacol. 1993 Dec;63(4):405-13.

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 800002110)

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000283)

REF 21

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005468)

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 800013080)

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 800003767)

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 800012535)

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 800001304)

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 800000110)

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 800010891)

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 800005292)

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 800000375)

REF 30

Electrophysiological actions of the pimobendan metabolite, UD-CG 212 Cl, in guinea pig myocardium. J Pharmacol Exp Ther. 1992 Jan;260(1):58-63.

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 800000057)

REF 32

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 33

In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. Anesthesiology. 2003 Apr;98(4):944-9.

REF 34

Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev. 2002 Fall;20(3):163-74.

REF 35

A phase II dose-ranging study of the phosphodiesterase inhibitor K-134 in patients with peripheral artery disease and claudication. J Vasc Surg. 2012 Feb;55(2):381-389.e1.

REF 36

K-134, a Phosphodiesterase 3 Inhibitor, Prevents Brain Damage by Inhibiting Thrombus Formation in a Rat Cerebral Infarction Model. PLoS One. 2012; 7(10): e46432.

REF 37

The presence of five cyclic nucleotide phosphodiesterase isoenzyme activities in bovine tracheal smooth muscle and the functional effects of select... Br J Pharmacol. 1991 Oct;104(2):471-7.

REF 38

Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials.Lancet Respir Med.2013 Nov;1(9):714-27.

REF 39

Company report (MediciNova)

REF 40

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 41

[The effect of phosphodiesterase type 3 inhibitor on chorio-retinal blood flow in rabbits eyes].Nippon Ganka Gakkai Zasshi.2002 Oct;106(10):615-20.

REF 42

Mechanism of action of OPC-8490 in human ventricular myocardium. Circulation. 1996 Feb 15;93(4):817-25.

REF 43

Effects of a novel cardiotonic agent, Org 9731, on force and aequorin light transients in intact ventricular myocardium of the dog: involvement of ... J Card Fail. 1995 Mar;1(2):143-53.

REF 44

The effects of various drugs on the myocardial inotropic response. Gen Pharmacol. 1995 Jan;26(1):1-31.

REF 45

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.PLoS One.2013;8(2):e56867.

REF 46

Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

REF 47

Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

REF 48

Inhibition of human cardiac cyclic AMP-phosphodiesterases by R 80122, a new selective cyclic AMP-phosphodiesterase III inhibitor: a comparison with other cardiotonic compounds. J Pharmacol Exp Ther. 1992 Oct;263(1):6-14.

REF 49

Hemodynamic effects of the novel selective cAMP-phosphodiesterase III inhibitor R 80122 in anesthetized patients with moderate left ventricular dys... J Cardiothorac Vasc Anesth. 1995 Jun;9(3):272-7.

REF 50

Studies on anti-allergic action of AH 21-132, a novel isozyme-selective phosphodiesterase inhibitor in airways. Jpn J Pharmacol. 1995 Feb;67(2):149-56.

REF 51

The phosphodiesterase 3 inhibitor ORG 9935 inhibits oocyte maturation in the naturally selected dominant follicle in rhesus macaques.Contraception.2008 Apr;77(4):303-7.

REF 52

[Effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase isozyme type III/IV inhibitor, on the release of histamine from human peripheral leukocytes].Arerugi.1997 May;46(5):426-32.

REF 53

Effects of inhaled SDZ ISQ 844, a cyclic nucleotide phosphodiesterase isoenzyme type III/IV inhibitor, on airway responsiveness in beagles. Arerugi. 1994 Apr;43(4):551-6.

REF 54

Cyclic-AMP-dependent proliferation of a human osteoblast cell line (HOS cells) induced by hydroxyapatite: effect of exogenous nitric oxide. Acta Biomed. 2008 Aug;79(2):110-6.

REF 55

Phosphodiesterase inhibition in ventricular cardiomyocytes from guinea-pig hearts. Br J Pharmacol. 1992 Sep;107(1):127-33.

REF 56

Contribution of cAMP-phosphodiesterase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan i... Circ Res. 1991 Mar;68(3):689-701.

REF 57

Zardaverine: a cyclic AMP specific PDE III/IV inhibitor.Agents Actions Suppl.1991;34:379-402.

REF 58

Phosphodiesterase 3 as a potential target for therapy of malignant tumors in the submandibular gland. Anticancer Drugs. 2001 Jan;12(1):79-83.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Feng ZHU

Prof. Yuzong CHEN