BMS-823778   Click here for help

GtoPdb Ligand ID: 10158

Synonyms: compound 2 [Li et al., 2018]
PDB Ligand
Compound class: Synthetic organic
Comment: BMS-823778 is an orally bioavailable clinical lead inhibitor of hydroxysteroid 11-beta dehydrogenase 1 (11β-HSD) [5] which is the enzyme that converts inactive cortisone to biologically active costisol [2]. We show the chemical structure for BMS-823778 free base. Some bioactivity data may have been determined using the hydrochloride salt (PubChem CID 54669979). BMS-823778 was developed for potential treatment of type 2 diabetes and metabolic syndrome.
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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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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 3
Topological polar surface area 50.42
Molecular weight 327.11
XLogP 5.57
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Clc1ccc(cc1)C1(CC1)c1nnc2n1cccc2C(O)(C)C
Isomeric SMILES Clc1ccc(cc1)C1(CC1)c1nnc2n1cccc2C(O)(C)C
InChI InChI=1S/C18H18ClN3O/c1-17(2,23)14-4-3-11-22-15(14)20-21-16(22)18(9-10-18)12-5-7-13(19)8-6-12/h3-8,11,23H,9-10H2,1-2H3
InChI Key PTIFVLOBVCIMKL-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Cheng Y, Wang L, Iacono L, Zhang D, Chen W, Gong J, Humphreys WG, Gan J. (2018)
Clinical significance of CYP2C19 polymorphisms on the metabolism and pharmacokinetics of 11β-hydroxysteroid dehydrogenase type-1 inhibitor BMS-823778.
Br J Clin Pharmacol, 84 (1): 130-141. [PMID:28850715]
2. Gathercole LL, Lavery GG, Morgan SA, Cooper MS, Sinclair AJ, Tomlinson JW, Stewart PM. (2013)
11β-Hydroxysteroid dehydrogenase 1: translational and therapeutic aspects.
Endocr Rev, 34 (4): 525-55. [PMID:23612224]
3. Gong J, Hansen L, Iacono L. (2018)
Clinical Pharmacokinetics and the Impact of Genetic Polymorphism on a CYP2C19 Substrate, BMS-823778, in Healthy Subjects.
Drug Metab Dispos, 46 (3): 316-325. [PMID:29311135]
4. Gong J, Iacono L, Iyer RA, Humphreys WG, Zheng M. (2018)
Physiologically-based pharmacokinetic modelling of a CYP2C19 substrate, BMS-823778, utilizing pharmacogenetic data.
Br J Clin Pharmacol, 84 (6): 1335-1345. [PMID:29469197]
5. Li J, Kennedy LJ, Walker SJ, Wang H, Li JJ, Hong Z, O'Connor SP, Ye XY, Chen S, Wu S et al.. (2018)
Discovery of Clinical Candidate BMS-823778 as an Inhibitor of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1).
ACS Med Chem Lett, 9 (12): 1170-1174. DOI: 10.1021/acsmedchemlett.8b00307 [PMID:30613321]