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

General Information of Drug (ID: DMU5RKC)

• Drug Name: SL65.0472 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 9869105
  CAS Number: CAS 189003-92-7
  TTD Drug ID: DMU5RKC

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 2A receptor (HTR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[4]
ZOTEPINE	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[5]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[6]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[7]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[8]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[9]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[10]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[11]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[12]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[13]

Drug(s) Affected By D(1A) dopamine receptor (DRD1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[14]
Haloperidol	DM96SE0	Delirium		Approved	[3]
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[15]
Pergolide mesylate	DM5GKOV	N. A.	N. A.	Approved	[16]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[3]
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[19]
Methamphetamine	DMPM4SK	Anxiety		Approved	[20]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[21]

Drug(s) Affected By D(4) dopamine receptor (DRD4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[22]
Haloperidol	DM96SE0	Delirium		Approved	[3]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[23]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[24]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Methamphetamine	DMPM4SK	Anxiety		Approved	[26]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[27]
Droperidol	DM0DXA8	Nausea	MD90	Approved	[14]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[14]

Drug(s) Affected By 5-hydroxytryptamine receptor 7 (HTR7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[28]
Cyproheptadine	DM92AH3	Allergic rhinitis	CA08.0	Approved	[29]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[29]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[30]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[31]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[32]
PD-0325901	DM27D4J	Breast cancer	2C60-2C65	Phase 2	[33]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[34]
SB-269970	DM8WTGA	Sleep-wake disorder	7A00-7B2Z	Terminated	[29]
ICI-169369	DMQ0IOF	Anxiety disorder	6B00-6B0Z	Terminated	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
5-hydroxytryptamine receptor 7 (HTR7)	OT44DEWB	5HT7R_HUMAN	Gene/Protein Processing	[3]
D(1A) dopamine receptor (DRD1)	OTLZPBT7	DRD1_HUMAN	Gene/Protein Processing	[3]
D(4) dopamine receptor (DRD4)	OTAJTO7N	DRD4_HUMAN	Gene/Protein Processing	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014358)
• [2] Antiplatelet and antithrombotic activity of SL65.0472, a mixed 5-HT1B/5-HT2A receptor antagonist.Thromb Haemost.2001 Mar;85(3):521-8.
• [3] Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95.
• [4] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [5] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [6] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [7] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [8] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [9] Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [11] Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
• [12] Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
• [13] Clinical pipeline report, company report or official report of Lundbeck.
• [14] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [15] Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry. 1992 Jul;49(7):538-44. doi: 10.1001/archpsyc.1992.01820070032005.
• [16] Pergolide is an inhibitor of voltage-gated potassium channels, including Kv1.5, and causes pulmonary vasoconstriction. Circulation. 2005 Sep 6;112(10):1494-9. doi: 10.1161/CIRCULATIONAHA.105.556704. Epub 2005 Aug 29.
• [17] Dopamine-mediated inhibition of renal Na+/K+-ATPase in HK-2 cells is reduced by ouabain. Clin Exp Pharmacol Physiol. 2010 May;37(5-6):613-8. doi: 10.1111/j.1440-1681.2010.05364.x. Epub 2010 Feb 4.
• [18] 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.
• [19] Characterizing fucoxanthin as a selective dopamine D(3)/D(4) receptor agonist: Relevance to Parkinson's disease. Chem Biol Interact. 2019 Sep 1;310:108757. doi: 10.1016/j.cbi.2019.108757. Epub 2019 Jul 16.
• [20] Dopamine D1 receptor protein is elevated in nucleus accumbens of human, chronic methamphetamine users. Mol Psychiatry. 2000 Nov;5(6):664-72. doi: 10.1038/sj.mp.4000760.
• [21] Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response. J Psychopharmacol. 2007 Sep;21(7):718-27. doi: 10.1177/0269881106072341. Epub 2006 Nov 8.
• [22] Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine. Int J Neurosci. 2005 Nov;115(11):1539-47. doi: 10.1080/00207450590957863.
• [23] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [24] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [25] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [26] Association analysis of the DRD4 and COMT genes in methamphetamine abuse. Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):120-4. doi: 10.1002/ajmg.b.30024.
• [27] Polymorphisms TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT: association with childhood ADHD in male African-Caribbean cocaine dependents?. Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1034-41. doi: 10.1002/ajmg.b.30540.
• [28] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [29] Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions. Psychopharmacology (Berl). 2010 Dec;212(4):687-97. doi: 10.1007/s00213-010-2001-x. Epub 2010 Sep 9.
• [30] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [31] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [32] Physiogenomic association of statin-related myalgia to serotonin receptors. Muscle Nerve. 2007 Sep;36(3):329-35. doi: 10.1002/mus.20871.
• [33] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [34] 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.