Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMGH3T5)

• Drug Name: ZAPRINAST Drug Info
• Cross-matching ID:
  PubChem CID: 135399235
  ChEBI ID: CHEBI:92215
  CAS Number: CAS 37762-06-4
  TTD Drug ID: DMGH3T5
  VARIDT Drug ID: DR00492

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 4D (PDE4D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Papaverine	DMCA9QP	Brain ischaemia	8B1Z	Approved	[5]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[6]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[7]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[8]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[9]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[10]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[7]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[11]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[12]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[11]

Drug(s) Targeting Phosphodiesterase 5A (PDE5A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tadalafil	DMJZHT1	Benign prostatic hyperplasia	GA90	Approved	[13]
Udenafil	DM1IQRP	Erectile dysfunction	HA01.1	Approved	[14]
Vardenafil	DMTBGW8	Cystic fibrosis	CA25	Approved	[15]
Dipyridamole	DMXY30O	Atrial fibrillation	BC81.3	Approved	[16]
Papaverine	DMCA9QP	Brain ischaemia	8B1Z	Approved	[17]
Avanafil	DM75CXN	Erectile dysfunction	HA01.1	Approved	[11]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[18]
ICARIIN	DMOJQGT	N. A.	N. A.	Phase 3	[19]
EXISULIND	DMBY56U	Colorectal cancer	2B91.Z	Phase 3	[20]
PF-489791	DM3C8GQ	Chronic obstructive pulmonary disease	CA22	Phase 2	[21]

Drug(s) Targeting Phosphodiesterase 1 (PDE1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vinpocetine	DMVN2E6	Ischemic stroke	8B11.5Z	Approved	[22]
ITI-214	DM08TH3	Parkinson disease	8A00.0	Phase 1/2	[23]
BIBW-22	DMXIH3Q	Solid tumour/cancer	2A00-2F9Z	Terminated	[24]
isobutylmethylxanthine	DM46F5X	Discovery agent	N.A.	Investigative	[25]
S,S-(2-Hydroxyethyl)Thiocysteine	DMLPAD8	Discovery agent	N.A.	Investigative	[26]
BUFROLIN	DM61F5W	Discovery agent	N.A.	Investigative	[25]

Drug(s) Affected By G-protein coupled receptor 35 (GPR35)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[28]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[29]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[30]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[31]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[32]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[33]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[34]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[35]
pamoic acid	DM7M5AF	Discovery agent	N.A.	Investigative	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 1 (PDE1)	TTHQENC	NOUNIPROTAC	Inhibitor	[1]
Phosphodiesterase 4D (PDE4D)	TTSKMI8	PDE4D_HUMAN	Inhibitor	[2]
Phosphodiesterase 5A (PDE5A)	TTJ0IQB	PDE5A_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
G-protein coupled receptor 35 (GPR35)	OTO23NRK	GPR35_HUMAN	Protein Interaction/Cellular Processes	[4]

References

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• [2] 8-Substituted analogues of 3-(3-cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine: highly potent and selective PDE4 inhibitors. J Med Chem. 2005 Feb 24;48(4):1237-43.
• [3] 4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity toward phosphodiesterase 5. J Med Chem. 2000 Jun 29;43(13):2523-9.
• [4] Antagonists of GPR35 display high species ortholog selectivity and varying modes of action. J Pharmacol Exp Ther. 2012 Dec;343(3):683-95. doi: 10.1124/jpet.112.198945. Epub 2012 Sep 11.
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• [12] 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.
• [13] Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
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• [15] The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. J Am Coll Cardiol. 2002 Dec 4;40(11):2006-12.
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• [17] Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. 2003 Mar;5(1):15-8.
• [18] cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium. J Pharmacol Exp Ther. 2009 Sep;330(3):884-91.
• [19] Potent inhibition of human phosphodiesterase-5 by icariin derivatives. J Nat Prod. 2008 Sep;71(9):1513-7.
• [20] Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res. 2000 Jul 1;60(13):3338-42.
• [21] Highlights of the society for medicinesresearch symposium held december 10th 2009 at the national heart and lung institute, London, UK. Drugs of the Future 2010, 35(4): 349-358.
• [22] Effects of phosphodiesterase inhibitors on contraction induced by endothelin-1 of isolated human prostatic tissue. Urology. 2009 Jun;73(6):1397-401.
• [23] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [24] BIBW22 BS, potent multidrug resistance-reversing agent, binds directly to P-glycoprotein and accumulates in drug-resistant cells. Mol Pharmacol. 1996 Sep;50(3):482-92.
• [25] A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity. J Med Chem. 1985 May;28(5):537-45.
• [26] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [27] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [28] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [29] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [30] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [31] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [32] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [33] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [34] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
• [35] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.