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

General Information of Drug (ID: DM95Z4Q)

• Drug Name: (R)-Rolipram Drug Info
• Synonyms: (R)-(-)-Rolipram; 85416-75-7; (R)-ROLIPRAM; (4R)-4-[3-(CYCLOPENTYLOXY)-4-METHOXYPHENYL]PYRROLIDIN-2-ONE; R-Rolipram; UNII-DPX51KUP08; DPX51KUP08; CHEMBL430893; CHEBI:40133; 1xmy; NCGC00016899-01; CAS-61413-54-5; Tocris-1349; Tocris-0905; Tocris-1350; PubChem18284; 1ro6; 3g4k; 1q9m; AC1L9LJS; Lopac-R-6520; SCHEMBL576805; ZINC4982; KS-00000QDB; MolPort-003-983-801; HMS3267P19; BCP14111

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 448055
  ChEBI ID: CHEBI:40133
  CAS Number: CAS 85416-75-7
  TTD Drug ID: DM95Z4Q

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 4B (PDE4B)

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

Drug(s) Targeting Phosphodiesterase 4 (PDE4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[10]
Oxtriphylline	DMLHSE3	Cough	MD12	Approved	[11]
Roflumilast	DMPGHY8	Asthma	CA23	Approved	[12]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[13]
crisaborole	DMNVKU6	Atopic dermatitis	EA80	Approved	[14]
Arofylline	DM84AD1	Chronic obstructive pulmonary disease	CA22	Phase 3	[15]
ARQ-151	DML61S4	Atopic dermatitis	EA80	Phase 3	[16]
SUN13834	DMPK34E	Gram-positive bacterial infection	1B74-1G40	Phase 2	[17]
ONO-6126	DMRT28X	Chronic obstructive pulmonary disease	CA22	Phase 2	[15]
E6005	DM1S489	Atopic dermatitis	EA80	Phase 2	[18]

Drug(s) Targeting Phosphodiesterase 4A (PDE4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dyphylline	DM8DZC1	Acute bronchial asthma	CA23	Approved	[17]
Enprofylline	DMFYZKN	Asthma	CA23	Approved	[19]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[2]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[20]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[21]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[5]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[6]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[7]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[20]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 4 (PDE4)	TTV5CGO	NOUNIPROTAC	Inhibitor	[1]
Phosphodiesterase 4A (PDE4A)	TTZ97H5	PDE4A_HUMAN	Inhibitor	[1]
Phosphodiesterase 4B (PDE4B)	TTVIAT9	PDE4B_HUMAN	Inhibitor	[1]

References

• [1] PDE4 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.
• [2] Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. J Med Chem. 2002 May 23;45(11):2342-5.
• [3] 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).
• [4] 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.
• [5] An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen. 2013 Jun;54(5):338-46.
• [6] Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 s... Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L196-204.
• [7] Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. Clin Exp Immunol. 2002 Jun;128(3):460-6.
• [8] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [9] 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.
• [10] Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [13] Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
• [14] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [15] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [16] Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.
• [17] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [18] Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
• [19] Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium. Am J Obstet Gynecol. 1987 Apr;156(4):958-62.
• [20] 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).
• [21] 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.
• [22] 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.