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

General Information of Drug (ID: DMYL7VR)

• Drug Name: Piclamilast Drug Info
• Synonyms: Piclamilast; 144035-83-6; Cpodpmb; RP 73401; 3-(Cyclopentyloxy)-N-(3,5-dichloropyridin-4-yl)-4-methoxybenzamide; UNII-WM58D7C3ZT; RP 73-401; RP-73401; RP-73-401; RPR 73401; 3-(Cyclopentyloxy)-N-(3,5-dichloro-4-pyridinyl)-4-methoxybenzamide; WM58D7C3ZT; Benzamide, 3-(cyclopentyloxy)-N-(3,5-dichloro-4-pyridinyl)-4-methoxy-; CHEMBL42126; CHEBI:47619; RRRUXBQSQLKHEL-UHFFFAOYSA-N; RPR-73401; 3-(Cyclopentyloxy)-N-(3,5-dichloro-4-pyridyl)-p-anisamide; 3-(Cyclopentyloxy)-N-(3,5-dichloro-4-pyridyl)-4-methoxybenzamide; PIL

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 154575
  ChEBI ID: CHEBI:47619
  CAS Number: CAS 144035-83-6
  TTD Drug ID: DMYL7VR

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	[4]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[5]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[6]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[7]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[8]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[9]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[6]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[10]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[11]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[10]

Drug(s) Targeting Phosphodiesterase 4B (PDE4B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[5]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[12]
BI 1015550	DM6DO2P	Idiopathic pulmonary fibrosis	CB03.4	Phase 3	[13]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[7]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[8]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[9]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[12]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[14]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[11]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[14]

Drug(s) Targeting Phosphodiesterase 4A (PDE4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dyphylline	DM8DZC1	Acute bronchial asthma	CA23	Approved	[15]
Enprofylline	DMFYZKN	Asthma	CA23	Approved	[16]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[5]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[17]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[18]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[7]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[8]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[9]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[17]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[19]

Drug(s) Affected By Cytochrome P450 2B6 (CYP2B6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[20]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[21]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[22]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[23]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[24]
Clopidogrel	DMOL54H	Acute coronary syndrome	BA41	Approved	[25]
Artemisinin	DMOY7W3	Malaria	1F40-1F45	Approved	[26]
Malathion	DMXZ84M	Pediculus capitis infestation	1G00.0	Approved	[27]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[28]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 4A (PDE4A)	TTZ97H5	PDE4A_HUMAN	Inhibitor	[2]
Phosphodiesterase 4B (PDE4B)	TTVIAT9	PDE4B_HUMAN	Inhibitor	[2]
Phosphodiesterase 4D (PDE4D)	TTSKMI8	PDE4D_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Regulation of Drug Effects	[3]

References

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• [2] 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.
• [3] Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes. Arch Biochem Biophys. 2003 Jan 1;409(1):32-44.
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• [5] Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. J Med Chem. 2002 May 23;45(11):2342-5.
• [6] 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. (Target id: 1303).
• [7] An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen. 2013 Jun;54(5):338-46.
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• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [11] 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.
• [12] 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. (Target id: 1301).
• [13] BI 1015550 is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis. Front Pharmacol. 2022 Apr 20;13:838449.
• [14] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [15] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [16] Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium. Am J Obstet Gynecol. 1987 Apr;156(4):958-62.
• [17] 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. (Target id: 1300).
• [18] 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.
• [19] GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54.
• [20] Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicol Lett. 2016 Jan 22;241:82-94.
• [21] Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 2016 Aug 5;255:31-44.
• [22] Evaluation of gene induction of drug-metabolizing enzymes and transporters in primary culture of human hepatocytes using high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. 2002 May;122(5):339-61.
• [23] Thalidomide increases human hepatic cytochrome P450 3A enzymes by direct activation of the pregnane X receptor. Chem Res Toxicol. 2014 Feb 17;27(2):304-308.
• [24] Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin. J Biol Chem. 2004 Jul 9;279(28):29295-301. doi: 10.1074/jbc.M400580200. Epub 2004 Apr 28.
• [25] Identification of novel agonists by high-throughput screening and molecular modelling of human constitutive androstane receptor isoform 3. Arch Toxicol. 2019 Aug;93(8):2247-2264. doi: 10.1007/s00204-019-02495-6. Epub 2019 Jul 16.
• [26] Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
• [27] Characterization of human cytochrome P450 induction by pesticides. Toxicology. 2012 Mar 29;294(1):17-26.
• [28] Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids. Arch Biochem Biophys. 2005 Feb 1;434(1):75-85.
• [29] Pyrethroids: cytotoxicity and induction of CYP isoforms in human hepatocytes. Drug Metabol Drug Interact. 2008;23(3-4):211-36.