| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
TRPA1 (transient receptor potential ankyrin 1) with IC50 of 17 nM. PF-04745637 is also a potent, selective small-molecule antagonist of the C-C chemokine receptor 2 (CCR2), blocking CCR2–CCL2 interactions and inhibiting monocyte recruitment and inflammatory signaling.
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| ln Vitro |
PF-04745637 is a potent and selective TRPA1 antagonist with an IC50 of 17 nM for human TRPA1. It also functions as a CCR2 antagonist, blocking CCR2–CCL2 interactions. Its high selectivity and pharmacological profile make it a valuable tool for studying chemokine-driven immune responses.
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| ln Vivo |
Applying PF-04745637 (Compound 8; 50 mg/mL and 100 mg/mL) topically to rat skin considerably decreased flares caused by cinnamaldehyde [1].
PF-04745637 (topically applied; 50 mg/mL and 100 mg/mL) significantly reduces cinnamaldehyde-mediated flare in rat skin. It has been investigated for therapeutic potential in conditions such as rheumatoid arthritis, atherosclerosis, and tumor microenvironment modulation. |
| Enzyme Assay |
TRPA1 antagonist activity assays are performed using cells expressing human TRPA1. Calcium influx is measured using fluorescent calcium indicators (Fluo-4) in response to TRPA1 agonists (e.g., cinnamaldehyde, AITC). PF-04745637 is applied at varying concentrations, and inhibition of agonist-induced calcium responses is measured. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate. CCR2 binding assays are performed using membranes from cells expressing recombinant CCR2 with radiolabeled ligands.
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| Cell Assay |
Cellular TRPA1 antagonism is evaluated in cell lines expressing human TRPA1 (e.g., HEK-293 cells). Cells are cultured in appropriate media and treated with PF-04745637 at various concentrations. Calcium influx is measured using fluorescent calcium indicators in response to TRPA1 agonists. The compound's antagonist activity is assessed by its ability to inhibit agonist-induced calcium responses. Cell viability is assessed using MTT or LDH assays. Each experiment includes known TRPA1 antagonists as positive controls and vehicle controls.
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| Animal Protocol |
In vivo efficacy is evaluated in rodent models of pain and inflammation. PF-04745637 is administered topically or systemically at doses determined by preclinical studies. The cinnamaldehyde-mediated flare model in rat skin is used to assess TRPA1 antagonism in vivo. Flare area is measured after topical application of cinnamaldehyde. The compound's ability to reduce flare is assessed. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 509.00. Formula: C27H32ClF3N2O2. CAS No.: 1917294-46-2. Purity: ≥95%. IUPAC Name: 1-(4-chlorophenyl)-N-[2-[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]-3-phenylpropyl]cyclopentane-1-carboxamide. For research use only.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available. As a TRPA1 and CCR2 antagonist, potential toxicities may include effects on pain sensation and immune function. Standard toxicity studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the nervous and immune systems. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References | |
| Additional Infomation |
PF-04745637 is also known as PF4745637. It is a potent and selective TRPA1 antagonist with an IC50 of 17 nM and a CCR2 antagonist. It has been investigated for rheumatoid arthritis, atherosclerosis, and tumor microenvironment modulation. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C27H32CLF3N2O2
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|---|---|
| Molecular Weight |
509.003396987915
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| Exact Mass |
508.21
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| CAS # |
1917294-46-2
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| PubChem CID |
121304823
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| Appearance |
White to off-white solid powder
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| LogP |
6.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
691
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)C1(C(NCC(CC2C=CC=CC=2)N2CCC(C(F)(F)F)(CC2)O)=O)CCCC1
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| InChi Key |
PAEBEJVPSADOMC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H32ClF3N2O2/c28-22-10-8-21(9-11-22)25(12-4-5-13-25)24(34)32-19-23(18-20-6-2-1-3-7-20)33-16-14-26(35,15-17-33)27(29,30)31/h1-3,6-11,23,35H,4-5,12-19H2,(H,32,34)
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| Chemical Name |
1-(4-chlorophenyl)-N-[2-[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]-3-phenylpropyl]cyclopentane-1-carboxamide
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| Synonyms |
PF04745637; PF 04745637; PF-04745637
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~245.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9646 mL | 9.8232 mL | 19.6464 mL | |
| 5 mM | 0.3929 mL | 1.9646 mL | 3.9293 mL | |
| 10 mM | 0.1965 mL | 0.9823 mL | 1.9646 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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