TBPB   Click here for help

GtoPdb Ligand ID: 3258

Compound class: Synthetic organic
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 44.27
Molecular weight 404.26
XLogP 3.54
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES Cc1ccccc1CN1CCC(CC1)N1CCC(CC1)n1c(=O)[nH]c2c1cccc2
Isomeric SMILES Cc1ccccc1CN1CCC(CC1)N1CCC(CC1)n1c(=O)[nH]c2c1cccc2
InChI InChI=1S/C25H32N4O/c1-19-6-2-3-7-20(19)18-27-14-10-21(11-15-27)28-16-12-22(13-17-28)29-24-9-5-4-8-23(24)26-25(29)30/h2-9,21-22H,10-18H2,1H3,(H,26,30)
InChI Key CWPKTBMRVATCBL-UHFFFAOYSA-N
References
1. Avlani VA, Langmead CJ, Guida E, Wood MD, Tehan BG, Herdon HJ, Watson JM, Sexton PM, Christopoulos A. (2010)
Orthosteric and allosteric modes of interaction of novel selective agonists of the M1 muscarinic acetylcholine receptor.
Mol Pharmacol, 78 (1): 94-104. [PMID:20413650]
2. Jakubík J, Bacáková L, El-Fakahany EE, Tucek S. (1997)
Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
Mol Pharmacol, 52 (1): 172-9. [PMID:9224827]
3. Jones CK, Brady AE, Davis AA, Xiang Z, Bubser M, Tantawy MN, Kane AS, Bridges TM, Kennedy JP, Bradley SR et al.. (2008)
Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats.
J Neurosci, 28 (41): 10422-33. [PMID:18842902]
4. Keov P, Valant C, Devine SM, Lane JR, Scammells PJ, Sexton PM, Christopoulos A. (2013)
Reverse engineering of the selective agonist TBPB unveils both orthosteric and allosteric modes of action at the M₁ muscarinic acetylcholine receptor.
Mol Pharmacol, 84 (3): 425-37. [PMID:23798605]
5. Langmead CJ, Austin NE, Branch CL, Brown JT, Buchanan KA, Davies CH, Forbes IT, Fry VA, Hagan JJ, Herdon HJ et al.. (2008)
Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1.
Br J Pharmacol, 154 (5): 1104-15. [PMID:18454168]
6. Langmead CJ, Fry VA, Forbes IT, Branch CL, Christopoulos A, Wood MD, Herdon HJ. (2006)
Probing the molecular mechanism of interaction between 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the muscarinic M(1) receptor: direct pharmacological evidence that AC-42 is an allosteric agonist.
Mol Pharmacol, 69 (1): 236-46. [PMID:16207821]
7. Richards MH, van Giersbergen PL. (1995)
Human muscarinic receptors expressed in A9L and CHO cells: activation by full and partial agonists.
Br J Pharmacol, 114 (6): 1241-9. [PMID:7620715]
8. Sams AG, Hentzer M, Mikkelsen GK, Larsen K, Bundgaard C, Plath N, Christoffersen CT, Bang-Andersen B. (2010)
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.
J Med Chem, 53 (17): 6386-97. [PMID:20684563]
9. Spalding TA, Ma JN, Ott TR, Friberg M, Bajpai A, Bradley SR, Davis RE, Brann MR, Burstein ES. (2006)
Structural requirements of transmembrane domain 3 for activation by the M1 muscarinic receptor agonists AC-42, AC-260584, clozapine, and N-desmethylclozapine: evidence for three distinct modes of receptor activation.
Mol Pharmacol, 70 (6): 1974-83. [PMID:16959945]
10. Spalding TA, Trotter C, Skjaerbaek N, Messier TL, Currier EA, Burstein ES, Li D, Hacksell U, Brann MR. (2002)
Discovery of an ectopic activation site on the M(1) muscarinic receptor.
Mol Pharmacol, 61 (6): 1297-302. [PMID:12021390]
11. Sur C, Mallorga PJ, Wittmann M, Jacobson MA, Pascarella D, Williams JB, Brandish PE, Pettibone DJ, Scolnick EM, Conn PJ. (2003)
N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity.
Proc Natl Acad Sci USA, 100 (23): 13674-9. [PMID:14595031]