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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.

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No. CAS: 1508276-29-6
Fòrmula: C₂₀H₁₃F₅KN₄O₃S₂
Peso molecular:555.56

Almacenamiento:

Please store the product under the recommended conditions in the Certificate of Analysis.

GRC-17536 Chemical Structure

No. CAS: 1508276-29-6

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Actividad biológica
- Descripciòn
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Pureza y Documentación
Referencias
Calculators
Help & FAQs
Classifications
Bioz

Actividad biológica

Descripciòn

GRC-17536 is a TRPA1 antagonist with selective inhibition of TRPA1-mediated calcium influx^[1]^[2]^[3]^[4].GRC-17536 binds to TRPA1 binding site 2 to inhibit channel activity^[3].GRC-17536 reduces irritant-induced cough responses and citric acid-induced cough responses^[2]^[4].GRC-17536 exhibits antitussive activity^[1]^[4].GRC-17536 has poor pharmacokinetic and bioavailability properties, leading to discontinued development after a Phase IIa study^[1]^[2].GRC-17536 can be used for the research of painful diabetic polyneuropathy, peripheral diabetic neuropathy, asthma, and chronic cough^[1]^[2]^[3]^[4].

IC₅₀ & Target

^[1]

TRPA1

Ver todos los productos específicos de isoformas TRP Channel :

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	IC50	6.8 μM	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.	36622903
CCD 19Lu	IC50	8.2 nM	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.	24819048
A549	IC50	5.0 nM	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.	24819048
CHO	IC50	4.6 nM	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.	24819048

In Vitro

OthersInnate Immunity

Others

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 TRPA1^N855S 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].

Innate Immunity

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.

In Vivo

GRC-17536 reduces cough responses in irritant-challenged guinea pigs^[2].
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.

Animal Model:

Hartley (male, 200-600 g)^[4]
Dosage:

30 mg/kg; 60 mg/kg; 100 mg/kg
Administration:

i.p.
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.

Related Protocols :

Chemical Information

No. CAS 1508276-29-6
Peso molecular 555.56
Fòrmula C₂₀H₁₃F₅KN₄O₃S₂
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
Envío

Room temperature in continental US; may vary elsewhere.
Almacenamiento

Please store the product under the recommended conditions in the Certificate of Analysis.

Pureza y Documentación

Instrucciones de manejo (2659 KB)

Referencias

[1]. Anand S, et al. A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain. Neuroscience insights. 2023;18:26331055231220340.

[2]. Chen H, et al. Transient receptor potential ankyrin 1 (TRPA1) antagonists: a patent review (2015-2019). Expert opinion on therapeutic patents. 2020 Sep;30(9):643-657. [Content Brief]

[3]. Mesch S, et al. Discovery of , a Selective CNS Penetrant Chemical Probe as Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonist. Journal of medicinal chemistry. 2023 Jan 26;66(2):1583-1600.

[4]. Mukhopadhyay I, et al. Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents: GRC 17536 as a promising anti-tussive therapeutic. PloS one. 2014;9(5):e97005.

Calculators

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Calculadora de dilución

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Bioz

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100 mg

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