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

General Information of Drug (ID: DMRBGI6)

• Drug Name: Torbafylline Drug Info
• Synonyms: Torbaphylline; HWA-448

Indication

Disease Entry	ICD 11	Status	REF
Peripheral vascular disease	BD4Z	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 65888
  CAS Number: CAS 105102-21-4
  TTD Drug ID: DMRBGI6

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	[2]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[3]
SOTB07	DMIG4OX	Asthma	CA23	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	[4]
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 4B (PDE4B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[3]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[10]
BI 1015550	DM6DO2P	Idiopathic pulmonary fibrosis	CB03.4	Phase 3	[11]
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	[10]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[12]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[9]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[12]

Drug(s) Targeting Phosphodiesterase 4A (PDE4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dyphylline	DM8DZC1	Acute bronchial asthma	CA23	Approved	[13]
Enprofylline	DMFYZKN	Asthma	CA23	Approved	[14]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[3]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[15]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[16]
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	[15]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[17]

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	[1]
Phosphodiesterase 4B (PDE4B)	TTVIAT9	PDE4B_HUMAN	Modulator	[1]
Phosphodiesterase 4D (PDE4D)	TTSKMI8	PDE4D_HUMAN	Modulator	[1]

References

• [1] Phosphodiesterase (PDE) inhibitor torbafylline (HWA 448) attenuates burn-induced rat skeletal muscle proteolysis through the PDE4/cAMP/EPAC/PI3K/Akt pathway. Mol Cell Endocrinol. 2014 Aug 5;393(1-2):152-63.
• [2] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [3] Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. J Med Chem. 2002 May 23;45(11):2342-5.
• [4] 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).
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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] 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).
• [11] 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.
• [12] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [13] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [14] Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium. Am J Obstet Gynecol. 1987 Apr;156(4):958-62.
• [15] 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).
• [16] 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.
• [17] 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.