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

General Information of Drug (ID: DMTGNWU)

• Drug Name: Tofisopam Drug Info
• Synonyms: tofisopam; 22345-47-7; Grandaxin; Seriel; 1-(3,4-Dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine; Egyt 341; Tofisopamum; 5H-2,3-Benzodiazepine, 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-; tofizopam; NCGC00165912-02; 1-(3,4-Dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-benzo[d][1,2]diazepine; benzodiazepine; EGYT 341; Grandaxin; Nodeprine; Seriel; Tofisopamum [INN-Latin]; 7,8-Dimethoxy-1-(3,4-dimethoxyphenyl)-5-ethyl-4-methyl-5H-2,3-benzodiazepine; Tofisopam [INN:DCF:JAN]; EINECS 244-922-3; CCRIS 8738; Emandaxin (TN); DSSTox_CID_3681; Tofisopam (JP17/INN); DSSTox_RID_77145; DSSTox_GSID_23681; SCHEMBL43522; Tofisopam (patented in japan); CHEMBL404216; SCHEMBL8086894; DTXSID3023681; CHEBI:32241; BCP09600; Tox21_112269; MFCD00823171; Tofisopam, >=98% (HPLC), solid; AKOS025401672; DB08811; QC-1212; NCGC00165912-01; NCGC00165912-03; AC-24288; LS-14948; CAS-22345-47-7; DB-045872; FT-0638212; X6663; D01254; 345T477; Q945537; Q-201839; BRD-A69095630-001-01-1; 1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiazepine; 1-[3,4-bis(methyloxy)phenyl]-5-ethyl-4-methyl-7,8-bis(methyloxy)-5H-2,3-benzodiazepine; (1Z,3Z)-1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-benzo[d][1,2]diazepine

Indication

Disease Entry	ICD 11	Status	REF
Hyperuricaemia	5C55.Y	Phase 2	[1]
Irritable bowel syndrome	DD91.0	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 5502
  ChEBI ID: CHEBI:32241
  CAS Number: CAS 22345-47-7
  TTD Drug ID: DMTGNWU

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 3 (PDE3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[4]
Oxtriphylline	DMLHSE3	Cough	MD12	Approved	[4]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[5]
Enoximone	DMQVZJD	Congestive heart failure	BD10	Approved	[6]
Olprinone	DMWBQKU	Heart failure	BD10-BD13	Approved	[7]
Inamrinone Lactate	DMRMFP4	Cardiac disease	BA00-BE2Z	Approved	[8]
Milrinone	DM8TUPF	Congestive heart failure	BD10	Approved	[4]
Tipelukast	DMS9BDQ	Asthma	CA23	Phase 2	[9]
RPL-554	DMLD4VQ	Allergic rhinitis	CA08.0	Phase 2	[10]
Org-30029	DMDZ4R2	Heart failure	BD10-BD13	Phase 2	[11]

Drug(s) Targeting Phosphodiesterase 4A (PDE4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dyphylline	DM8DZC1	Acute bronchial asthma	CA23	Approved	[12]
Enprofylline	DMFYZKN	Asthma	CA23	Approved	[13]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[14]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[15]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[16]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[17]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[18]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[15]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[19]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[20]

Drug(s) Targeting Phosphodiesterase 2A (PDE2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CP-461	DMEYMTX	Inflammatory bowel disease	DD72	Phase 2	[21]
ND7001	DMUBTC6	Mood disorder	6A60-6E23	Phase 1	[22]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[23]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2	DM4CSBD	N. A.	N. A.	Patented	[23]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 2	DMS3ROL	N. A.	N. A.	Patented	[23]
Triazolo-pyridine derivative 5	DM1R205	N. A.	N. A.	Patented	[23]
PMID27321640-Compound-58	DM0NYK3	N. A.	N. A.	Patented	[23]
Triazolo-pyridine derivative 4	DM5ZQKS	N. A.	N. A.	Patented	[23]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 3	DMZ61T8	N. A.	N. A.	Patented	[23]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 4	DMKR5ZO	N. A.	N. A.	Patented	[23]

Drug(s) Targeting Phosphodiesterase 10A (PDE10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TAK-063	DMP1873	Schizophrenia	6A20	Phase 2	[24]
PF-02545920	DMJPE61	Huntington disease	8A01.10	Phase 2	[25]
OMS824	DMA4OGL	Huntington disease	8A01.10	Phase 2	[26]
Lu AF11167	DMJOYNZ	Schizophrenia	6A20	Phase 2	[27]
FRM-6308	DMNCOE1	Schizophrenia	6A20	Phase 1b	[28]
PBF-999	DMBSQH9	Huntington disease	8A01.10	Phase 1	[29]
RG7203	DMYX4NP	Schizophrenia	6A20	Phase 1	[30]
AMG 579	DMRMC7U	Schizophrenia	6A20	Phase 1	[31]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[23]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2	DM4CSBD	N. A.	N. A.	Patented	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 10A (PDE10)	TTJW4LU	PDE10_HUMAN	Inhibitor	[3]
Phosphodiesterase 2A (PDE2A)	TTJGW1Z	PDE2A_HUMAN	Inhibitor	[3]
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Inhibitor	[3]
Phosphodiesterase 4A (PDE4A)	TTZ97H5	PDE4A_HUMAN	Inhibitor	[3]

References

• [1] ClinicalTrials.gov (NCT01519687) Study of Levotofisopam 50 mg Three Times a Day (TID) Administered for 7 Days on Hyperuricemia and Gout. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT00486876) A Study of 3 Doses of Dextofisopam in Females With Irritable Bowel Syndrome. U.S. National Institutes of Health.
• [3] 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.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
• [6] In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. Anesthesiology. 2003 Apr;98(4):944-9.
• [7] Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev. 2002 Fall;20(3):163-74.
• [8] Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8.
• [9] Company report (MediciNova)
• [10] 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.
• [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.
• [12] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [13] Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium. Am J Obstet Gynecol. 1987 Apr;156(4):958-62.
• [14] Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. J Med Chem. 2002 May 23;45(11):2342-5.
• [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] An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen. 2013 Jun;54(5):338-46.
• [17] 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.
• [18] 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.
• [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] 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.
• [21] Sulindac and its derivatives: a novel class of anticancer agents. Curr Opin Investig Drugs. 2001 May;2(5):677-83.
• [22] Phosphodiesterase 2 inhibitors promote axonal outgrowth in organotypic slice co-cultures. Neurosignals. 2013;21(3-4):197-212.
• [23] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.
• [24] Characterization of Binding and Inhibitory Properties of TAK-063, a Novel Phosphodiesterase 10A Inhibitor. PLoS One. 2015; 10(3): e0122197.
• [25] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [26] New Drugs/Drug News. P T. 2013 November; 38(11): 667-672.
• [27] PDE10A Inhibitors-Clinical Failure or Window Into Antipsychotic Drug Action?. Front Neurosci. 2021 Jan 20;14:600178.
• [28] Massive schizophrenia genomics study offers new drug directions. Nat Rev Drug Discov. 2014 Sep;13(9):641-2.
• [29] Clinical pipeline report, company report or official report of Palobiofarma.
• [30] Synaptic synopsis. SciBX 6(41); doi:10.1038/scibx.2013.1153. Oct. 24, 2013
• [31] Discovery of clinical candidate 1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone (AMG 579), a potent, selective, and efficacious inhibitor of phosphodiesterase10A (PDE10A). J Med Chem. 2014 Aug 14;57(15):6632-41.