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| 5mg |
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Purity: ≥98%
JNJ-17203212 is a novel, potent, reversible, competitive and selective TRPV1 antagonist with IC50 of 65 nM and 102 nM for human TRPV1 and rat TRPV1. JNJ-17203212 inhibits capsaicin- and H+-induced channel activation (pIC50 values are 6.32 and 7.23 respectively) and exhibits antitussive and analgesic activity in vivo. JNJ-17203212, reduces sensitivity to luminal distension in both an acute, noninflammatory and a chronic, post-inflammatory rodent model of colonic hypersensitivity. These data indicate that TRPV1 is involved in the pathogenesis of visceral hypersensitivity and that JNJ-17203212 may be a potential therapeutic agent for functional bowel disorders characterized by abdominal hypersensitivity, such as irritable bowel syndrome.
| Targets |
In TRPV1-expressing HEK cells, imperatorin-induced TRPV1 activation (Ca2+ rise) is significantly inhibited by JNJ-17203212 (0.5 μM) [1].
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| ln Vitro |
In TRPV1-expressing HEK cells, imperatorin-induced TRPV1 activation (Ca2+ rise) is significantly inhibited by JNJ-17203212 (0.5 μM) [1].
JNJ-17203212 (500 nM) effectively inhibited capsaicin (20 nM)-induced intracellular Ca²⁺ increases in human TRPV1-expressing HEK (TRPV1-HEK) cells.[1] JNJ-17203212 (500 nM) completely inhibited intracellular Ca²⁺ transients induced by 10 μM imperatorin in TRPV1-HEK cells.[1] The compound decreased the basal level of fluorescence in TRPV1-expressing HEK cells, indicating suppression of spontaneous TRPV1 activity in this overexpression model.[1] |
| ln Vivo |
The early gene c-fos's expression is elevated by inflammatory soup (IS) and is dose-dependently reduced by JNJ-17203212 (0.3 mg/kg; iv) [2]. JNJ-17203212, in a dose-dependent manner, fully inhibits the release of CGRP (neurotransmitter calcitonin gene-related peptide) caused by capsaicin [2].
JNJ-17203212 dose-dependently reduces inflammatory soup (IS)-induced c-fos expression in the trigeminal nucleus caudalis (TNC), with complete abolition at 30 mg/kg. [2] JNJ-17203212 dose-dependently blocks capsaicin-induced CGRP release in jugular vein blood, completely abolishing release at 30 mg/kg within 10 minutes. [2] |
| Enzyme Assay |
pIC50 values were determined using recombinant hTRPV1 in a Ca²⁺ influx assay (FLIPR). [2]
pKi values were determined by radioligand binding to a broad panel of receptors, channels, and transporters. [2] |
| Cell Assay |
Fluorescence imaging experiments were performed to assess the effect of JNJ-17203212 on TRPV1-mediated Ca²⁺ influx. HEK cells transiently expressing human TRPV1 were loaded with Fura-2AM (4 μM) in a calcium- and magnesium-containing PBS buffer for 1 hour, followed by a 30-minute incubation in dye-free buffer. Single-cell intracellular Ca²⁺ changes were monitored using a fluorescence imaging system. Cells were continuously superfused with test solutions. The standard extracellular solution contained 145 mM NaCl, 2.5 mM KCl, 1.2 mM CaCl₂, 1 mM MgCl₂, 10 mM HEPES, and 5.5 mM glucose (pH 7.2). To test JNJ-17203212, cells were pretreated or co-treated with the compound (500 nM) before or during application of agonists like capsaicin or imperatorin. The inhibition of agonist-induced Ca²⁺ transients was measured.[1]
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (260-300 g) [2]
Doses: 0.3 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: The increase in c-fos expression after intracisternal injection of IS was dose-dependent Influence. Male Sprague–Dawley rats (260–300 g) were anesthetized with thiopental-sodium (60 mg/kg i.p.), tracheotomized, and mechanically ventilated. Femoral artery and vein were cannulated for blood pressure monitoring and intravenous drug administration. [2] For c-fos study: A catheter was placed into the cisterna magna for inflammatory soup (IS) administration. JNJ-17203212 or vehicle was administered intravenously over 20 minutes before IS injection. Animals were perfused 2 hours post-IS for c-fos immunohistochemistry. [2] For CGRP study: The external jugular vein and carotid artery were cannulated. JNJ-17203212 was administered intravenously over 20 minutes before capsaicin injection into the carotid artery. Blood samples were taken at 5, 10, and 15 minutes post-capsaicin for CGRP measurement. [2] Doses used: 0.3, 3, and 30 mg/kg i.v. [2] |
| ADME/Pharmacokinetics |
The half-life of JNJ-17203212 is 7.4 hours. [2] Its oral bioavailability is 14% higher than that of SB-705498. [2]
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| References | |
| Additional Infomation |
This study refers to JNJ-17203212 as a specific TRPV1 antagonist and uses it as a pharmacological tool to demonstrate that the action of the natural product isoprenone is mediated through the TRPV1 channel. [1]
This study did not study JNJ-17203212 itself as a primary candidate drug; its data are presented in the context of elucidating the mechanism of action of isoprenone. [1] |
| Molecular Formula |
C17H15F6N5O
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| Molecular Weight |
419.324323892593
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| Exact Mass |
419.118
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| CAS # |
821768-06-3
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| PubChem CID |
11339118
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.944
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
29
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| Complexity |
564
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JFRYYGVYCWYIDQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15F6N5O/c18-16(19,20)11-3-4-13(25-10-11)26-15(29)28-8-6-27(7-9-28)14-12(17(21,22)23)2-1-5-24-14/h1-5,10H,6-9H2,(H,25,26,29)
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| Chemical Name |
1-Piperazinecarboxamide, 4-(3-(trifluoromethyl)-2-pyridinyl)-N-(5-(trifluoromethyl)-2-pyridinyl)-
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| Synonyms |
JNJ-17203212; JNJ 17203212; JNJ17203212.
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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 : ≥ 100 mg/mL (~238.48 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (6.56 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 27.5 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 | 2.3848 mL | 11.9241 mL | 23.8481 mL | |
| 5 mM | 0.4770 mL | 2.3848 mL | 4.7696 mL | |
| 10 mM | 0.2385 mL | 1.1924 mL | 2.3848 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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