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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2D Structure
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Physico-chemical Properties
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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
SMILES / InChI / InChIKey
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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
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
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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 pIC50 - 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.