Therapeutic Targets Database
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Target Validation Information
TTD IDTTDS00004
Target NameMuscarinic acetylcholine receptor M3    
Type of TargetSuccessful target    
Drug Potency against TargetSuccinylcholineIC50 = 123000 nM[1]
AtropineKi = 0.5 nM[2]
DarifenacinKi = 1.58 nM[2]
PirenzepineKi = 125 nM[2]
SuccinylcholineKi = 18450 nM[3]
OxybutyninKi = 5.01 nM[2]
TolterodineKi = 6.3 nM[2]
1,1-diphenyl-2-(3-tropanyl)ethanolIC50 < 10 nM[4]
Tiotropium BromideIC50 = 0.35 nM[5]
SULFOARECOLINEIC50 = 1.4 nM[6]
7-Dimethylamino-3-methyl-hept-5-yn-2-oneIC50 = 101 nM[7]
N-methoxyquinuclidine-3-carboximidoyl chlorideIC50 = 1100 nM[8]
7-Pyrrolidin-1-yl-hept-5-yn-2-one oximeIC50 = 1254 nM[7]
CREMASTRINEIC50 = 126 nM[9]
6-Dimethylamino-2-methyl-hex-4-ynal oximeIC50 = 13230 nM[7]
7-Dimethylamino-hept-5-yn-2-one oximeIC50 = 139 nM[7]
1'-Benzyl-3-phenyl-[3,4']bipiperidinyl-2,6-dioneIC50 = 15 nM[10]
3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octaneIC50 = 16000 nM[11]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oximeIC50 = 1928 nM[7]
N-methoxyquinuclidine-3-carboximidoyl fluorideIC50 = 2000 nM[8]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamideIC50 = 21.6 nM[7]
BRL-55473IC50 = 470 nM[8]
ISOLOXAPINEIC50 = 49 nM[12]
ACECLIDINEIC50 = 510 nM[13]
ISOCLOZAPINEIC50 = 55 nM[14]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-oneIC50 = 5696 nM[7]
7-Dimethylamino-hept-5-yn-2-oneIC50 = 68 nM[7]
7-Pyrrolidin-1-yl-hept-5-yn-2-oneIC50 = 7280 nM[7]
FLUMEZAPINEIC50 = 80 nM[15]
XANOMELINEIC50 = 9.7 nM[16]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-oneKi < 1000 nM[17]
nocardimicin CKi = 1000 nM[18]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-ureaKi = 10700 nM[19]
Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl esterKi = 11400 nM[20]
NOCARDIMICIN AKi = 1250 nM[18]
GNF-PF-5618Ki = 130 nM[18]
Nocardimicin FKi = 1330 nM[18]
nocardimicin DKi = 230 nM[18]
FM1-10Ki = 24 nM[21]
UCB-101333-3Ki = 3.2 nM[22]
FM1-43Ki = 30 nM[21]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl esterKi = 440 nM[20]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-oneKi = 6.7 nM[23]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl esterKi = 680 nM[24]
N-DESMETHYLCLOZAPINEKi = 90 nM[17]
Noccardimicin EKi = 970 nM[18]
Action against Disease ModelTiotropiumTiotropi uM concentration-dependently inhibited pulmonary neutrophilic inflammation with IC50: 0.058 mg/mL[25]
OxybutyninpKi in Chinese Hamster Ovary M3 receptors/Cynomolgus monkey bladder smooth muscles: 7.12/8.7[26]
Ref 1Anesthesiology. 1998 Mar;88(3):744-50.Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. To Reference
Ref 2Trends Pharmacol Sci. 2001 Aug;22(8):409-14.Therapeutic opportunities from muscarinic receptor research. To Reference
Ref 3Curr Top Med Chem. 2004;4(3):361-8.Receptor binding thermodynamics at the neuronal nicotinic receptor. To Reference
Ref 4Bioorg Med Chem Lett. 2009 Aug 15;19(16):4560-2. Epub 2009 Jul 8.Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide as an efficacious inhaled muscarinic acetylcholine receptor antagonist for the treatment of COPD. To Reference
Ref 5J Med Chem. 2009 Aug 27;52(16):5076-92.Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters as potent and long-acting muscarinic antagonists with potential for minimal systemic exposure after inhaled administration: identification of (3R)-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (aclidinium bromide). To Reference
Ref 6J Med Chem. 1988 Jul;31(7):1312-6.Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. To Reference
Ref 7Bioorg. Med. Chem. Lett. 2(8):803-808 (1992) To Reference
Ref 8Bioorg. Med. Chem. Lett. 2(8):791-796 (1992) To Reference
Ref 9J Nat Prod. 2005 Apr;68(4):572-3.Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. To Reference
Ref 10J Med Chem. 1989 May;32(5):1057-62.Synthesis and biological evaluation of [125I]- and [123I]-4-iododexetimide, a potent muscarinic cholinergic receptor antagonist. To Reference
Ref 11J Med Chem. 1992 Apr 3;35(7):1280-90.Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. To Reference
Ref 12J Med Chem. 1981 Sep;24(9):1021-6.Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. To Reference
Ref 13J Med Chem. 1993 Apr 2;36(7):842-7.Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. To Reference
Ref 14J Med Chem. 1990 Feb;33(2):809-14.Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. To Reference
Ref 15J Med Chem. 1989 Dec;32(12):2573-82.Synthesis and pharmacological evaluation of a series of 4-piperazinylpyrazolo[3,4-b]- and -[4,3-b][1,5]benzodiazepines as potential anxiolytics. To Reference
Ref 16Bioorg. Med. Chem. Lett. 2(8):809-814 (1992) To Reference
Ref 17J 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 18J Nat Prod. 2005 Jul;68(7):1061-5.Nocardimicins A, B, C, D, E, and F, siderophores with muscarinic M3 receptor inhibiting activity from Nocardia sp. TP-A0674. To Reference
Ref 19J Med Chem. 1992 Aug 21;35(17):3270-9.Urea and 2-imidazolidone derivatives of the muscarinic agents oxotremorine and N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide. To Reference
Ref 20J Med Chem. 2000 Jun 29;43(13):2514-22.6beta-Acyloxy(nor)tropanes: affinities for antagonist/agonist binding sites on transfected and native muscarinic receptors. To Reference
Ref 21Bioorg Med Chem Lett. 2008 Jan 15;18(2):825-7. Epub 2007 Nov 17.Design and synthesis of a fluorescent muscarinic antagonist. To Reference
Ref 22Bioorg Med Chem Lett. 2007 Jun 1;17(11):3077-80. Epub 2007 Mar 19.Dual M3 antagonists-PDE4 inhibitors. Part 2: Synthesis and SAR of 3-substituted azetidinyl derivatives. To Reference
Ref 23J Med Chem. 1998 Oct 22;41(22):4181-5.Synthesis and modeling studies of a potent conformationally rigid muscarinic agonist: 1-azabicyclo[2.2.1]heptanespirofuranone. To Reference
Ref 24J Med Chem. 1998 Jun 4;41(12):2047-55.6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. To Reference
Ref 25Rat C6 glioma cells contain type I as well as type II corticosteroid receptors. Brain Research. Volume 342, Issue 2, 9 September 1985, Pages 252-258 To Reference
Ref 26J Pharmacol Exp Ther. 2004 Sep;310(3):1255-65. Epub 2004 May 12.Functional selectivity of muscarinic receptor antagonists for inhibition of M3-mediated phosphoinositide responses in guinea pig urinary bladder and submandibular salivary gland. To Reference



 

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