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

General Information of Drug (ID: DMM61Y2)

• Drug Name: BRL-15572 Drug Info
• Synonyms: BRL15572; BRL-15,572; BRL 15572

Indication

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

• Cross-matching ID:
  PubChem CID: 3654103
  ChEBI ID: CHEBI:64060
  CAS Number: CAS 734517-40-9
  TTD Drug ID: DMM61Y2

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 1B receptor (HTR1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[3]
Eletriptan	DMW649X	Migraine	8A80	Approved	[4]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[4]
Frovatriptan	DM7RE8P	Migraine	8A80	Approved	[4]
Fluphenazine	DMIT8LX	Psychotic disorder	6A20-6A25	Approved	[4]
Naratriptan	DMO50U2	Migraine	8A80	Approved	[5]
Prolixin decanoate	DMMJ1IS	Schizophrenia	6A20	Approved	[4]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[6]
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[7]
[N-methyl-3H(3)]AZ-10419369	DMSCV02	Mood disorder	6A60-6E23	Phase 1	[8]

Drug(s) Targeting 5-HT 1D receptor (HTR1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[9]
Eletriptan	DMW649X	Migraine	8A80	Approved	[4]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[4]
Frovatriptan	DM7RE8P	Migraine	8A80	Approved	[4]
Sumatriptan	DMVYXR8	Migraine	8A80	Approved	[10]
Rizatriptan	DMDJMA3	Migraine	8A80	Approved	[11]
Almogran	DM7I64Z	Migraine	8A80	Approved	[12]
Neu-P11	DMIQDFW	Alzheimer disease	8A20	Phase 2	[13]
FKB01MD	DM2O7NM	N. A.	N. A.	Phase 2	[14]
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[7]

Drug(s) Targeting 5-HT 6 receptor (HTR6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LU AE58054	DMWGRQD	Schizophrenia	6A20	Phase 3	[15]
SB-742457	DM6L4ZT	Alzheimer disease	8A20	Phase 3	[16]
AVN 211	DMVB4OS	Schizophrenia	6A20	Phase 2/3	[17]
SYN120	DMDF7XB	Parkinson disease	8A00.0	Phase 2	[18]
AVN 101	DMJFLBC	Alzheimer disease	8A20	Phase 2	[17]
SYN-120	DMPW0UL	Alzheimer disease	8A20	Phase 2	[19]
PF-05212377	DMPVQYR	Alzheimer disease	8A20	Phase 2	[20]
AVN 322	DMK2LGM	Cognitive impairment	6D71	Phase 2	[16]
SAM-531	DMHVJZ6	Alzheimer disease	8A20	Phase 2	[21]
SUVN-502	DMQD753	Alzheimer disease	8A20	Phase 2	[22]

Drug(s) Targeting 5-HT 2B receptor (HTR2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[23]
Triflupromazine	DMKFQJP	Psychotic disorder	6A20-6A25	Approved	[24]
Minaprine	DM0EP7M	Depression	6A70-6A7Z	Approved	[25]
SPN-812	DMTV7XH	Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[26]
Vabicaserin	DM9GZW6	Psychotic disorder	6A20-6A25	Phase 2	[27]
PRX-08066	DMR7H2V	Pulmonary arterial hypertension	BB01.0	Phase 2	[28]
Pyrimidine derivative 29	DMVOYJ8	N. A.	N. A.	Patented	[29]
Pyrimidine derivative 26	DM90WKN	N. A.	N. A.	Patented	[29]
Pyrimidine derivative 23	DM5MLQU	N. A.	N. A.	Patented	[29]
Pyrimidine derivative 25	DM51MFS	N. A.	N. A.	Patented	[29]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[23]
Zotepine	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[30]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[31]
Flibanserin	DM70DTN	Mood disorder	6A60-6E23	Approved	[32]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[33]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[34]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[35]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[36]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[37]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[38]

Drug(s) Targeting 5-HT 1F receptor (HTR1F)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[39]
Lasmiditan	DMXLVDT	Migraine	8A80	Approved	[40]
LY-334370	DM43O9N	Migraine	8A80	Phase 2	[41]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[39]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[42]
1-naphthylpiperazine	DM6BIWK	Discovery agent	N.A.	Investigative	[39]
2-methyl-5-HT	DM1S5CB	N. A.	N. A.	Investigative	[42]
alpha-methyl-5-HT	DMCAYXF	Discovery agent	N.A.	Investigative	[42]
WAY-466	DMMOH51	Discovery agent	N.A.	Investigative	[43]
[125I]LSD	DMP69QG	Discovery agent	N.A.	Investigative	[44]

Drug(s) Targeting 5-HT 1A receptor (HTR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[4]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[45]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[46]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[47]
Flibanserin	DM70DTN	Mood disorder	6A60-6E23	Approved	[32]
Tertatolol	DM2L3D5	Hypertension	BA00-BA04	Approved	[48]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[49]
Treximet	DMU54QB	Migraine	8A80	Approved	[50]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[51]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[6]

Drug(s) Targeting 5-HT 2C receptor (HTR2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[23]
Lorcaserin	DMG6OYJ	Obesity	5B81	Approved	[52]
Tramadol	DMRQD04	Pain	MG30-MG3Z	Approved	[53]
Mirtazapine	DML53ZJ	Depression	6A70-6A7Z	Approved	[54]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[55]
Methysergide	DM1EF73	Migraine	8A80	Approved	[56]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[6]
M100907	DM7ZFBA	Sleep-wake disorder	7A00-7B2Z	Phase 3	[57]
SR46349B	DM1ODMR	Primary insomnia	7A00	Phase 3	[58]
Vabicaserin	DM9GZW6	Psychotic disorder	6A20-6A25	Phase 2	[27]

Drug(s) Targeting 5-HT 1E receptor (HTR1E)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[59]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[59]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[59]
1-naphthylpiperazine	DM6BIWK	Discovery agent	N.A.	Investigative	[59]
2-methyl-5-HT	DM1S5CB	N. A.	N. A.	Investigative	[42]
alpha-methyl-5-HT	DMCAYXF	Discovery agent	N.A.	Investigative	[59]
m-chlorophenylpiperazine	DMM1J2D	Discovery agent	N.A.	Investigative	[59]
EDMT	DMS3AXK	Discovery agent	N.A.	Investigative	[60]
9-OH-risperidone	DMGORXQ	Discovery agent	N.A.	Investigative	[61]
[3H]5-HT	DMYJXV7	Discovery agent	N.A.	Investigative	[62]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Agonist	[2]
5-HT 1B receptor (HTR1B)	TTK8CXU	5HT1B_HUMAN	Agonist	[2]
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Agonist	[2]
5-HT 1E receptor (HTR1E)	TTCPG9S	5HT1E_HUMAN	Agonist	[2]
5-HT 1F receptor (HTR1F)	TT0MI3F	5HT1F_HUMAN	Agonist	[2]
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Agonist	[2]
5-HT 2B receptor (HTR2B)	TT0K1SC	5HT2B_HUMAN	Agonist	[2]
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Agonist	[2]
5-HT 6 receptor (HTR6)	TTJS8PY	5HT6R_HUMAN	Agonist	[2]

References

• [1] 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. (Ligand id: 10).
• [2] SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20.
• [3] Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors. J Neurochem. 1996 Nov;67(5):2096-103.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Triptans in pregnancy. Ther Drug Monit. 2008 Feb;30(1):5-9.
• [6] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [7] Company report (NeurAxon)
• [8] 5-HT1B and other related serotonergic proteins are altered in APPswe mutation. Neurosci Lett. 2015 May 6;594:137-43.
• [9] Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8.
• [10] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [11] An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210.
• [12] Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clin Ther. 2001 Nov;23(11):1867-75.
• [13] Clinical pipeline report, company report or official report of Neurim Pharmaceuticals.
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33.
• [16] 5-HT6 receptors and Alzheimer's disease. Alzheimers Res Ther. 2013; 5(2): 15.
• [17] Latrepirdine, a potential novel treatment for Alzheimer's disease and Huntington's chorea. Curr Opin Investig Drugs. 2010 January; 11(1): 80-91.
• [18] Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs. Nat Rev Drug Discov. 2018 Nov;17(11):804-822.
• [19] The Serotonin-6 Receptor as a Novel Therapeutic Target. Exp Neurobiol. 2011 December; 20(4): 159-168.
• [20] PF-05212377 Alzheimer's Disease (Phase 2). Pfizer.
• [21] Activation of 5-HT6 receptors modulates sleep-wake activity and hippocampal theta oscillation. ACS Chem Neurosci. 2013 Jan 16;4(1):191-9.
• [22] Novel and Potent 5-Piperazinyl Methyl-N1-aryl Sulfonyl Indole Derivatives as 5-HT6 Receptor Ligands. ACS Med Chem Lett. 2010 October 14; 1(7): 340-344.
• [23] 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.
• [24] Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharmacol. 1979 Sep;67(1):79-85.
• [25] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [26] New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300.
• [27] Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model.CPT Pharmacometrics Syst Pharmacol.2014 Apr 23;3:e111.
• [28] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [29] Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.
• [30] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [31] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [32] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [33] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [34] 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.
• [35] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [36] 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.
• [37] 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.
• [38] Clinical pipeline report, company report or official report of Lundbeck.
• [39] Cloning and characterization of the guinea pig 5-HT1F receptor subtype: a comparison of the pharmacological profile to the human species homolog. Neuropharmacology. 1997 Apr-May;36(4-5):569-76.
• [40] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [41] Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial. Lancet. 2001 Oct 13;358(9289):1230-4.
• [42] Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408-12.
• [43] Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists. J Med Chem. 2005 Jan 27;48(2):353-6.
• [44] Isolation of a mouse "5HT1E-like" serotonin receptor expressed predominantly in hippocampus. J Biol Chem. 1992 Oct 5;267(28):19761-4.
• [45] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [46] Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
• [47] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [48] Synthesis of new derivatives of 8-OH-DPAT: Influence of substitution on the aromatic ring on the pharmacological profile, Bioorg. Med. Chem. Lett. 3(10):2035-2038 (1993).
• [49] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [50] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [51] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [52] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [53] The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
• [54] Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
• [55] Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
• [56] Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats. Respir Physiol Neurobiol. 2008 May 31;161(3):230-8.
• [57] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [58] SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology. 2002 Sep;27(3):430-41.
• [59] Molecular cloning and pharmacological characterization of the guinea pig 5-HT1E receptor. Eur J Pharmacol. 2004 Jan 26;484(2-3):127-39.
• [60] 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000 Mar 9;43(5):1011-8.
• [61] Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73.
• [62] Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5517-21.