GRC-17536
GRC-17536 is a TRPA1 antagonist with selective inhibition of TRPA1-mediated calcium influx.GRC-17536 binds to TRPA1 binding site 2 to inhibit channel activity.GRC-17536 reduces irritant-induced cough responses and citric acid-induced cough responses.GRC-17536 exhibits antitussive activity.GRC-17536 has poor pharmacokinetic and bioavailability properties, leading to discontinued development after a Phase IIa study.GRC-17536 can be used for the research of painful diabetic polyneuropathy, peripheral diabetic neuropathy, asthma, and chronic cough.
For research use only. We do not sell to patients.
- CAS No.: 1649479-05-9
- Formula: C20H13F5KN4O3S2
- Molecular Weight:555.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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TRPA1 |
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Cell Line
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Type | Value | Description | References |
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| CHO | IC50 |
6.8 μM
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Inhibition of wild-type human TRPA1-mediated calcium flux in transiently transfected CHO GCaMP6 cells assessed via FLIPR Tetra calcium fluorescence assay with 10 min incubation of GRC-17536 prior to cinnamaldehyde addition, with fluorescence measured for 2 min post-agonist addition.
Inhibition of wild-type human TRPA1-mediated calcium flux in transiently transfected CHO GCaMP6 cells assessed via FLIPR Tetra calcium fluorescence assay with 10 min incubation of GRC-17536 prior to cinnamaldehyde addition, with fluorescence measured for 2 min post-agonist addition.
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36622903 |
| CCD 19Lu | IC50 |
8.2 nM
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Inhibition of citric acid-induced calcium influx in human lung fibroblast CCD19-Lu cells assessed by calcium influx assay with 15 minutes pre-incubation prior to agonist addition.
Inhibition of citric acid-induced calcium influx in human lung fibroblast CCD19-Lu cells assessed by calcium influx assay with 15 minutes pre-incubation prior to agonist addition.
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24819048 |
| A549 | IC50 |
5.0 nM
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Inhibition of citric acid-induced calcium influx in human pulmonary alveolar epithelial A549 cells assessed by calcium influx assay with 15 minutes pre-incubation prior to agonist addition.
Inhibition of citric acid-induced calcium influx in human pulmonary alveolar epithelial A549 cells assessed by calcium influx assay with 15 minutes pre-incubation prior to agonist addition.
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24819048 |
| CHO | IC50 |
4.6 nM
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Inhibition of citric acid-induced calcium influx in Chinese hamster ovary cells stably expressing human TRPA1 (hTRPA1/CHO) assessed by calcium influx assay with 15 minutes pre-incubation prior to agonist addition.
Inhibition of citric acid-induced calcium influx in Chinese hamster ovary cells stably expressing human TRPA1 (hTRPA1/CHO) assessed by calcium influx assay with 15 minutes pre-incubation prior to agonist addition.
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24819048 |
GRC-17536 (0.8 nM-25 μM; 10 min) inhibits wild-type human TRPA1-mediated calcium flux in transiently transfected CHO GCaMP6 cells with an IC50 of 6.8 μM[3].
GRC-17536 (0.8 nM-25 μM; 10 min) binds to human TRPA1 site 2, as indicated by a large potency shift at the TRPA1N855S mutant, with no significant shifts at other tested mutants[3].
GRC-17536 (15 min) potently inhibits citric acid-induced calcium influx in human lung fibroblast CCD19-Lu cells with an IC50 of 8.2 nM[4].
GRC-17536 (15 min) potently inhibits citric acid-induced calcium influx in human pulmonary alveolar epithelial A549 cells with an IC50 of 5.0 nM[4].
GRC-17536 (15 min) potently inhibits citric acid-induced calcium influx in hTRPA1/CHO cells with an IC50 of 4.6 nM[4].
GRC-17536 (1 μM) is highly selective for TRPA1, showing minimal inhibition of human TRPV1, TRPV3, TRPV4, and TRPM8 receptors at 1 μM[4].
GRC-17536 (10 nM - 1 μM) inhibits TLR ligand-enhanced, AITC-induced calcium uptake in hTRPA1/CHO cells, achieving ~50% inhibition at 10 nM and near-complete inhibition at 1 μM[4].
GRC-17536 (10 nM - 1 μM) inhibits TLR ligand-enhanced, AITC-induced calcium uptake in human pulmonary alveolar epithelial A549 cells, achieving ~40-68% inhibition at 10 nM and near-complete inhibition at 1 μM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GRC-17536 (30-100 mg/kg; i.p.) inhibits citric acid-induced cough in guinea pigs in a dose-dependent manner, achieving 89% inhibition at 100 mg/kg[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Hartley (male, 200-600 g)[4]
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Dosage:30 mg/kg; 60 mg/kg; 100 mg/kg
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Administration:i.p.
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Result:Showed no significant cough inhibition at 30 mg/kg.
Inhibited citric acid-induced cough by 79% at 60 mg/kg.
Inhibited citric acid-induced cough by 89% at 100 mg/kg.
Reached a free mean plasma concentration around its in vitro IC50 value at 100 mg/kg.
Chemical Information
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CAS No. 1649479-05-9
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Molecular Weight 555.56
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Formula C20H13F5KN4O3S2
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SMILES
[K].O=C1C2=C(SC=C2CC(=O)NC3=NC(=CS3)C=4C=CC(F)=C(C4F)C(F)(F)F)N(C(=O)N1C)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GRC-17536 Related Classifications
HY-187618 Related Classifications
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