TTD Target ID: TTDS00399

Target Information
Name	5-hydroxytryptamine receptor 3A
Type of target	Successful target
Synonyms	5-HT-3
	5-HT3A
	5-HT3R
	5HT3R
	HTR3
	HTR3A
	Serotonin receptor 3A
	Serotonin-gated ion channel receptor
Disease	Chemotherapy-induced nausea and vomiting    [1]
	Diarrhea    [2]
	Irritable bowel syndrome    [3]
	Postoperative nausea and vomiting    [4]
Drug(s)	Alosetron		Approved	Irritable bowel syndrome	[3][2]
	Dolasetron		Approved	Nausea and vomiting	[1]
	Levetriacetam		Approved	Fibromyalgia	[5]
	Palonosetron		Approved	Nausea and vomiting	[4]
	Procaine		Approved	Anesthetic	[6]
	Tropisetron		Approved	Fibromyalgia	[5]
	Renzapride		Phase III completed	Irritable bowel syndrome	[7]
	Arverapamil		Phase II completed	Irritable bowel syndrome	[7]
	DDP-225		Phase II	Irritable bowel syndrome	[7]
	DDP-225		Terminated in Phase II	Chronic functional vomiting	[7]
	ATI-17000		Preclinical	Irritable bowel syndrome	[7]
BioChemical Class	Ion transport
UniProt ID	P46098
Sequence	MLLWVQQALLALLLPTLLAQGEARRSRNTTRPALLRLSDYLLTNYRKGVRPVRDWRKPTT VSIDVIVYAILNVDEKNQVLTTYIWYRQYWTDEFLQWNPEDFDNITKLSIPTDSIWVPDI LINEFVDVGKSPNIPYVYIRHQGEVQNYKPLQVVTACSLDIYNFPFDVQNCSLTFTSWLH TIQDINISLWRLPEKVKSDRSVFMNQGEWELLGVLPYFREFSMESSNYYAEMKFYVVIRR RPLFYVVSLLLPSIFLMVMDIVGFYLPPNSGERVSFKITLLLGYSVFLIIVSDTLPATAI GTPLIGVYFVVCMALLVISLAETIFIVRLVHKQDLQQPVPAWLRHLVLERIAWLLCLREQ STSQRPPATSQATKTDDCSAMGNHCSHMGGPQDFEKSPRDRCSPPPPPREASLAVCGLLQ ELSSIRQFLEKRDEIREVARDWLRVGSVLDKLLFHIYLLAVLAYSITLVMLWSIWQYA
Target Validation	Click to Find Target Validation Information.
Inhibitor	(4-Quinolin-2-ylpiperazin-1-yl)acetic Acid		[8]
	1- (biphenyl-4-yl)-3-		[9]
	10,11-dihydro-5H-dibenzo[b,f]azepine		[10]
	2- (1H-Imidazol-4-ylmethyl)-4-phenyl-thiazole		[11]
	2- (4-Benzyl-piperazin-1-yl)-benzothiazole		[12]
	2- (4-Methyl-piperazin-1-yl)-quinoline		[13]
	3- (2-Amino-ethyl)-2-methyl-1H-indol-5-ol		[11]
	3alpha- (1'-Methyl-2'-Indolecarbonyloxy)-tropane		[14]
	3alpha- (2'-Indolecarbonyloxy)-nortropane		[14]
	4- (		[15]
	4- (4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one		[16]
	4-Benzoxazo-2-yl-1,4-diazabicyclo[3.2.2]nonane		[17]
	5,6-dichloro-3,4-dihydroquinazolin-2-amine		[18]
	5-chloro-3,4-dihydroquinazolin-2-amine		[18]
	6- (4-Methyl-piperazin-1-yl)-phenanthridine		[13]
	7- (piperidin-4-ylmethoxy)-2-naphthonitrile		[15]
	A-987306		[19]
	BEMESETRON		[20]
	BRL-24682		[21]
	BRL-46470		[22]
	CP-810123		[17]
	FLUPENTIXOLE		[10]
	MESULERGINE		[23]
	ML-10302		[24]
	Norcisapride		[25]
	PH-709829		[26]
	PHA-543613		[26]
	QUIPAZINE		[27]
	SC-52491		[28]
	SC-53116		[28]
	SDZ-205557		[24]
	SEROTONIN		[13]
	ZACOPRIDE		[24]
Antagonist	AS-8112		[29]
	ATI-17000		[7]
	Alosetron		[3][2]
	Arverapamil		[7]
	CR-3124		[29]
	DDP-225		[7]
	Dolasetron		[1]
	Levetriacetam		[5]
	Palonosetron		[4]
	Procaine		[6]
	Renzapride		[7]
	Tropisetron		[5]
Multitarget	Renzapride		[7]
Cross References	3D Structure Related Literature On-Line Medical Dictionary
Ref 1	Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 2009 Feb;10(2):115-24. Epub 2009 Jan 8. To Reference
Ref 2	Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta. 2009 May;403(1-2):47-55. Epub 2009 Feb 4. To Reference
Ref 3	Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844. Epub 2009 May 26. To Reference
Ref 4	Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34. Epub 2009 Mar 26. To Reference
Ref 5	Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62. To Reference
Ref 6	Local anesthetics have different mechanisms and sites of action at recombinant 5-HT3 receptors. Reg Anesth Pain Med. 2007 Nov-Dec;32(6):462-70. To Reference
Ref 7	Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313. To Reference
Ref 8	J Med Chem. 2009 Jun 11;52(11):3548-62.Specific targeting of peripheral serotonin 5-HT(3) receptors. Synthesis, biological investigation, and structure-activity relationships. To Reference
Ref 9	J Med Chem. 2010 Jun 10;53(11):4379-89.Novel alpha-7 nicotinic acetylcholine receptor agonists containing a urea moiety: identification and characterization of the potent, selective, and orally efficacious agonist 1-[6-(4-fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1-ylbutyl) urea (SEN34625/WYE-103914). To Reference
Ref 10	Eur J Med Chem. 2009 Jun;44(6):2667-72. Epub 2008 Dec 16.Molecular properties of psychopharmacological drugs determining non-competitive inhibition of 5-HT3A receptors. To Reference
Ref 11	J Med Chem. 1990 Jan;33(1):13-6.Aromatic thiazole derivatives: structurally novel and selective serotonin-3 receptor antagonists. To Reference
Ref 12	J Med Chem. 1994 Apr 29;37(9):1320-5.Synthesis of 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives with 5-HT3 antagonist and 5-HT4 agonist properties. To Reference
Ref 13	J Med Chem. 1999 May 6;42(9):1556-75.Novel potent and selective central 5-HT3 receptor ligands provided with different intrinsic efficacy. 2. Molecular basis of the intrinsic efficacy of arylpiperazine derivatives at the central 5-HT3 receptors. To Reference
Ref 14	Bioorg Med Chem. 2009 Oct 1;17(19):6872-8. Epub 2009 Aug 20.Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors. To Reference
Ref 15	Bioorg Med Chem Lett. 2009 Apr 15;19(8):2329-32. Epub 2009 Feb 20.Design and optimization of selective serotonin re-uptake inhibitors with high synthetic accessibility. Part 1. To Reference
Ref 16	J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 17	J Med Chem. 2010 Feb 11;53(3):1222-37.Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models. To Reference
Ref 18	Bioorg Med Chem Lett. 2008 Jan 1;18(1):256-61. Epub 2007 Oct 30.Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation. To Reference
Ref 19	J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia. To Reference
Ref 20	J Med Chem. 1992 Jan 24;35(2):310-9.Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. To Reference
Ref 21	J Med Chem. 2003 Feb 27;46(5):702-15.Synthesis and structure-affinity relationships of novel N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides with potent serotonin 5-HT3 and dopamine D2 receptor antagonistic activity. To Reference
Ref 22	J Med Chem. 1997 Oct 10;40(21):3369-80.Phenylimidazolidin-2-one derivatives as selective 5-HT3 receptor antagonists and refinement of the pharmacophore model for 5-HT3 receptor binding. To Reference
Ref 23	J Med Chem. 1997 Oct 24;40(22):3670-8.Novel and highly potent 5-HT3 receptor agonists based on a pyrroloquinoxaline structure. To Reference
Ref 24	Bioorg. Med. Chem. Lett. 4(12):1433-1436 (1994) To Reference
Ref 25	Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83. Epub 2009 Aug 8.mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). To Reference
Ref 26	Bioorg Med Chem Lett. 2008 Jun 15;18(12):3611-5. Epub 2008 May 1.Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity. To Reference
Ref 27	J Med Chem. 2009 Nov 12;52(21):6946-50.Novel, potent, and selective quinoxaline-based 5-HT(3) receptor ligands. 1. Further structure-activity relationships and pharmacological characterization. To Reference
Ref 28	J Med Chem. 2006 Feb 9;49(3):1125-39.Pyrrolizidine esters and amides as 5-HT4 receptor agonists and antagonists. To Reference
Ref 29	Emerging drugs for chemotherapy-induced emesis. Expert Opin Emerg Drugs. 2006 Mar;11(1):137-51. To Reference

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Professor in Department of Pharmacy
National University of Singapore, Singapore

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