Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameMuscarinic acetylcholine receptor M1    
Type of TargetSuccessful target    
Drug Potency against TargetBenztropineIC50 = 0.294 nM[1]
EthopropazineIC50 = 257000 nM[2]
AtropineKi = 1 nM[3]
DarifenacinKi = 15.8 nM[3]
TolterodineKi = 3.98 nM[3]
PirenzepineKi = 6.3 nM[3]
OxybutyninKi = 6.3 nM[3]
GSK1034702KD = 0.1 nM[4]
1,1-diphenyl-2-(3-tropanyl)ethanolIC50 < 10 nM[5]
Tiotropium BromideIC50 = 0.22 nM[6]
7-Dimethylamino-3-methyl-hept-5-yn-2-oneIC50 = 101 nM[8]
N-methoxyquinuclidine-3-carboximidoyl chlorideIC50 = 1100 nM[9]
7-Pyrrolidin-1-yl-hept-5-yn-2-one oximeIC50 = 1254 nM[8]
6-Dimethylamino-2-methyl-hex-4-ynal oximeIC50 = 13230 nM[8]
7-Dimethylamino-hept-5-yn-2-one oximeIC50 = 139 nM[8]
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]
SB-202026IC50 = 170 nM[12]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oximeIC50 = 1928 nM[8]
N-methoxyquinuclidine-3-carboximidoyl fluorideIC50 = 2000 nM[9]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamideIC50 = 21.6 nM[8]
BI-1356IC50 = 295 nM[13]
BRL-55473IC50 = 470 nM[9]
CREMASTRINEIC50 = 505 nM[15]
ACECLIDINEIC50 = 510 nM[16]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-oneIC50 = 5696 nM[8]
7-Dimethylamino-hept-5-yn-2-oneIC50 = 68 nM[8]
7-Pyrrolidin-1-yl-hept-5-yn-2-oneIC50 = 7280 nM[8]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-oneKi < 1000 nM[20]
CARAMIPENKi = 1.21 nM[22]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-ureaKi = 10700 nM[23]
Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl esterKi = 190 nM[25]
R-dimethindeneKi = 2.4 nM[26]
2-(4-Diethylamino-but-2-ynyl)-isoindole-1,3-dioneKi = 30 nM[27]
FM1-10Ki = 34 nM[28]
3alpha-(bis-chloro-phenylmethoxy)tropaneKi = 40.6 nM[24]
FM1-43Ki = 44 nM[28]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl esterKi = 440 nM[25]
HIMBACINEKi = 48 nM[29]
GNF-PF-5618Ki = 490 nM[30]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl esterKi = 5.6 nM[31]
RR(17)PZKi = 53.5 nM[32]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-oneKi = 6.7 nM[33]
Bo(15)PZKi = 69.7 nM[32]
Action against Disease ModelPirenzepineAffinity for the muscarinic receptors in the cerebral cortex IC50: 14 nM[34]
TrihexyphenidylAffinity for the muscarinic receptors in the cerebral cortex IC50: 3.7 nM[34]
DicyclomineAffinity for the muscarinic receptors in the cerebral cortex(rat) IC50: 5.1 nM[34]
GlycopyrrolateIC50 of EFS-induced contraction in Guinea pig/h uMan trachea: 0.15 nM/0.44 nM[35]
Ref 1J Pharmacol Exp Ther. 2004 May;309(2):650-60. Epub 2004 Jan 30.Effects of N-substituted analogs of benztropine: diminished cocaine-like effects in dopamine transporter ligands. To Reference
Ref 2Comp Biochem Physiol B Biochem Mol Biol. 2008 Mar;149(3):401-9. Epub 2007 Nov 9.Acetylcholinesterase in the sea urchin Lytechinus variegatus: characterization and developmental expression in larvae. To Reference
Ref 3Trends Pharmacol Sci. 2001 Aug;22(8):409-14.Therapeutic opportunities from muscarinic receptor research. To Reference
Ref 4Mini Rev Med Chem. 2007 Jan;7(1):79-86.Recent advances in the development of agonists selective for beta1-type thyroid hormone receptor. To Reference
Ref 5Bioorg 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 6J 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 7J Med Chem. 1988 Jul;31(7):1312-6.Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. To Reference
Ref 8Bioorg. Med. Chem. Lett. 2(8):803-808 (1992) To Reference
Ref 9Bioorg. Med. Chem. Lett. 2(8):791-796 (1992) 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. 1997 Dec 19;40(26):4265-80.Design of [R-(Z)]-(+)-alpha-(methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitri le (SB 202026), a functionally selective azabicyclic muscarinic M1 agonist incorporating the N-methoxy imidoyl nitrile group as a novel ester bioisostere. To Reference
Ref 13J Med Chem. 2007 Dec 27;50(26):6450-3. Epub 2007 Dec 1.8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. To Reference
Ref 14J 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 15J Nat Prod. 2005 Apr;68(4):572-3.Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. To Reference
Ref 16J 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 17J 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 18J Med Chem. 1992 Oct 30;35(22):4011-9.Novel functional M1 selective muscarinic agonists. 2. Synthesis and structure-activity relationships of 3-pyrazinyl-1,2,5,6-tetrahydro-1-methylpyridines. Construction of a molecular model for the M1 pharmacophore. To Reference
Ref 19J 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 20J 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 21J Med Chem. 1997 Mar 14;40(6):851-7.3'-Chloro-3 alpha-(diphenylmethoxy)tropane but not 4'-chloro-3 alpha-(diphenylmethoxy)tropane produces a cocaine-like behavioral profile. To Reference
Ref 22J Med Chem. 1991 Oct;34(10):2984-9.Muscarinic receptor binding profile of para-substituted caramiphen analogues. To Reference
Ref 23J 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 24J Med Chem. 2006 Oct 19;49(21):6391-9.Structure-activity relationship studies on a novel series of (S)-2beta-substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for in vivo investigation. To Reference
Ref 25J 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 26J Med Chem. 2009 Sep 10;52(17):5307-10.Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia. To Reference
Ref 27Bioorg. Med. Chem. Lett. 7(8):979-984 (1997) To Reference
Ref 28Bioorg 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 29Bioorg Med Chem Lett. 2004 Aug 2;14(15):3967-70.Himbacine analogs as muscarinic receptor antagonists--effects of tether and heterocyclic variations. To Reference
Ref 30J 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 31J Med Chem. 1998 Jun 4;41(12):2047-55.6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. To Reference
Ref 32J Med Chem. 2005 Dec 1;48(24):7847-59.On the use of nonfluorescent dye labeled ligands in FRET-based receptor binding studies. To Reference
Ref 33J 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 34Br J Pharmacol. 1986 Sep;89(1):83-90.Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine. To Reference
Ref 35Br J Pharmacol. 1999 May;127(2):413-20.Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways. To Reference


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