SH045   Click here for help

GtoPdb Ligand ID: 9968

Synonyms: compound 19 [PMID: 29522264]
Compound class: Synthetic organic
Comment: SH045 is a TRPC6 channel blocker [1]. It is a synthetic congener of the diterpene natural product (+)‐larixol (PubChem CID 11335788), which is found in the resin of the European larch, Larix decidua. In vitro and ex vivo studies suggest SH045 as a lead compound with clinical potential for the reduction of lung ischemia‐reperfusion edema (LIRE).
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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 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 58.56
Molecular weight 363.28
XLogP 5.33
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 CNC(=O)OC1CC(=C)C(C2(C1C(C)(C)CCC2)C)CCC(C=C)(O)C
Isomeric SMILES CNC(=O)O[C@H]1CC(=C)[C@@H]([C@@]2([C@@H]1C(C)(C)CCC2)C)CC[C@@](C=C)(O)C
InChI InChI=1S/C22H37NO3/c1-8-21(5,25)13-10-16-15(2)14-17(26-19(24)23-7)18-20(3,4)11-9-12-22(16,18)6/h8,16-18,25H,1-2,9-14H2,3-7H3,(H,23,24)/t16-,17-,18-,21+,22+/m0/s1
InChI Key VDWLBNKHHJKPOQ-LDAQOBCYSA-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/)
Bioactivity Comments
SH045 blocks inward and outward currents through TRPC6, 3 and 7 in patch‐clamp electrophysiological whole‐cell assays:
TRPC6 inward IC50 5.8 nM; outward IC50 5.2 nM
TRPC3 inward IC50 440 nM; outward IC50 634 nM
TRPC7 inward IC50 22 nM; outward IC50 18 nM.
SH045 exhibits high selectivity over TRPA1 (630‐fold), TRPV1 (400‐fold) and TRPM2 (1400‐fold) and it does not significantly alter activity of the other tested channels including TRPC4, 5 and TRPV2, TRPV3, TRPM3, and TRPM8 [1].
Selectivity at ion channels
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
TRPC6 Hs Channel blocker - 7.2 pIC50 - 1
⤷ pIC50 7.2 (IC50 6.3x10-8 M) [1]
Description: Measuring inhibition of calcium flux in HEK293 cells expressing hTRPC6, in a FLIPR assay.
TRPC7 Hs Channel blocker - 6.7 – 7.7 pIC50 - 1
⤷ pIC50 ~7.7 (IC50 ~2x10-8 M) [1]
pIC50 6.7 (IC50 2.2x10-7 M) [1]
Description: Measuring inhibition of calcium flux in HEK293 cells expressing hTRPC7, in a FLIPR assay.
TRPC3 Hs Channel blocker - 6.1 pIC50 - 1
⤷ pIC50 6.1 (IC50 8.4x10-7 M) [1]
Description: Measuring inhibition of calcium flux in HEK293 cells expressing hTRPC3, in a FLIPR assay.