NPS 2143   Click here for help

GtoPdb Ligand ID: 716

Synonyms: NPS-2143 | NPS2143
PDB Ligand
Compound class: Synthetic organic
Comment: NPS 2143 is a calcilytic molecule, acting as an antagonist at the calcium-sensing receptor (CaSR). It demonstrates antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) [1].
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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 2
Rotatable bonds 8
Topological polar surface area 65.28
Molecular weight 408.16
XLogP 5.24
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 N#Cc1c(cccc1Cl)OCC(CNC(Cc1ccc2c(c1)cccc2)(C)C)O
Isomeric SMILES N#Cc1c(cccc1Cl)OC[C@@H](CNC(Cc1ccc2c(c1)cccc2)(C)C)O
InChI InChI=1S/C24H25ClN2O2/c1-24(2,13-17-10-11-18-6-3-4-7-19(18)12-17)27-15-20(28)16-29-23-9-5-8-22(25)21(23)14-26/h3-12,20,27-28H,13,15-16H2,1-2H3/t20-/m1/s1
InChI Key PZUJQWHTIRWCID-HXUWFJFHSA-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. Chen Y, Ju Y, Li C, Yang T, Deng Y, Luo Y. (2019)
Design, synthesis, and antibacterial evaluation of novel derivatives of NPS-2143 for the treatment of methicillin-resistant S. aureus (MRSA) infection.
J Antibiot (Tokyo), 72 (7): 545-554. [PMID:30940910]
2. Davey AE, Leach K, Valant C, Conigrave AD, Sexton PM, Christopoulos A. (2012)
Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor.
Endocrinology, 153 (3): 1232-41. [PMID:22210744]
3. Faure H, Gorojankina T, Rice N, Dauban P, Dodd RH, Bräuner-Osborne H, Rognan D, Ruat M. (2009)
Molecular determinants of non-competitive antagonist binding to the mouse GPRC6A receptor.
Cell Calcium, 46 (5-6): 323-32. [PMID:19836834]
4. Hellyer SD, Albold S, Wang T, Chen ANY, May LT, Leach K, Gregory KJ. (2018)
"Selective" Class C G Protein-Coupled Receptor Modulators Are Neutral or Biased mGlu5 Allosteric Ligands.
Mol Pharmacol, 93 (5): 504-514. [PMID:29514854]
5. Leach K, Gregory KJ, Kufareva I, Khajehali E, Cook AE, Abagyan R, Conigrave AD, Sexton PM, Christopoulos A. (2016)
Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor.
Cell Res, 26 (5): 574-92. [PMID:27002221]
6. Leach K, Wen A, Cook AE, Sexton PM, Conigrave AD, Christopoulos A. (2013)
Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators.
Endocrinology, 154 (3): 1105-16. [PMID:23372019]
7. Nemeth EF, Delmar EG, Heaton WL, Miller MA, Lambert LD, Conklin RL, Gowen M, Gleason JG, Bhatnagar PK, Fox J. (2001)
Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone.
J Pharmacol Exp Ther, 299 (1): 323-31. [PMID:11561095]
8. Yang W, Wang Y, Roberge JY, Ma Z, Liu Y, Michael Lawrence R, Rotella DP, Seethala R, Feyen JH, Dickson Jr JK. (2005)
Discovery and structure-activity relationships of 2-benzylpyrrolidine-substituted aryloxypropanols as calcium-sensing receptor antagonists.
Bioorg Med Chem Lett, 15 (4): 1225-8. [PMID:15686947]