| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
JYL1421 targets the transient receptor potential vanilloid 1 (TRPV1) receptor, a non-selective cation channel activated by capsaicin, heat, and protons. TRPV1 plays a key role in nociception (pain sensation) and thermoregulation. JYL1421 acts as a competitive antagonist at the capsaicin-binding site of TRPV1, blocking receptor activation and downstream signaling.
|
|---|---|
| ln Vitro |
Capsaicin (330 nM)-induced Ca2+ buildup was concentration-dependently reduced by JYL 1421 incubation for 5 minutes. At the lowest dose (5 nM), JYL 1421's inhibitory action became significant, and at 1 μM, the response was nearly completely abolished, with just 3.1 ± 0.65% of the initial Ca2+ influx caused by capsaicin being seen. The IC50 value of JYL 1421 is 8 nM. Meanwhile, capsaicin had a much lower effect, only producing 41.7% inhibition at 1 μM; nevertheless, this inhibition did not rise to 50% at 10 μM or higher [1].
In vitro, JYL1421 inhibits capsaicin-induced calcium uptake in CHO cells expressing rat TRPV1 with an EC50 of 9.2 nM. It concentration-dependently reduces capsaicin (330 nM)-induced Ca²⁺ accumulation with an IC50 of 8 nM. JYL1421 also inhibits capsaicin-induced release of neuropeptides (somatostatin, substance P, and CGRP) from isolated rat trachea with IC50 values of 227-491 nM. Unlike several other TRPV1 antagonists, JYL1421 does not induce hyperthermia in rats at doses ranging from 1.02 to 32.77 μmol/kg. |
| ln Vivo |
After dripping 50 μL of capsaicin solution (10 μg/mL) into the rat's left eye, the animal wiped 12.9 ± 1.3 times in just three minutes. Rats' wiping behavior was not substantially affected by pretreatment with 0.4 or 1 mg/kg ip JYL 1421; however, the number of wiping movements was dose-dependently decreased with 2–5 mg/kg. A value of 4.6 mg/kg is the ID50. Rats without treatment had a mean arterial pressure of 109.9±4.2 Hgmm (n=6). When 1 and 2 μg/kg capsaicin were injected intravenously, the subjects' blood pressure temporarily dropped to 47.4±4.7 and 59.6±4.2 Hgmm, respectively (n=6). In both cases, JYL 1421 did not result in hypotension (0.4 and 1.6 mg/kg). The requirement for greater capsaicin dosages to produce reflex hypotension after JYL 1421 administration than before to treatment indicates that JYL 1421 dose-dependently suppresses the drops in blood pressure that capsaicin causes. Even at dosages as high as 2 mg/kg, capsaicin is unable to substantially prevent capsaicin-induced hypotension [1].
In vivo, JYL1421 significantly reduces capsaicin-evoked nocifensive eye-wiping behavior in rats in a dose-dependent manner. It inhibits capsaicin-induced hypothermia and hypotension in rats when administered at doses of 2 and 0.4 mg/kg, respectively. JYL1421 (2 mg/kg) also reduces the number of wiping movements induced by ocular administration of capsaicin in rats. It effectively attenuates capsaicin-induced reflex hypotension without affecting baseline blood pressure. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for TRPV1 antagonists typically involve radioligand binding assays using [³H]resiniferatoxin (RTX) as a high-affinity TRPV1 ligand. Membranes prepared from cells expressing recombinant TRPV1 are incubated with the radioligand and varying concentrations of JYL1421. Specific binding is determined by subtracting non-specific binding (defined by excess unlabeled RTX or capsaicin). IC50 values are calculated from competition curves. Functional assays measure capsaicin-induced ⁴⁵Ca²⁺ uptake or FLIPR-based calcium flux assays in TRPV1-expressing cells.
|
| Cell Assay |
Cellular assays for JYL1421 typically use CHO cells stably or transiently expressing rat or human TRPV1. Cells are loaded with calcium-sensitive fluorescent dyes (e.g., Fluo-4 or Fura-2) and stimulated with capsaicin (typically 330 nM) in the presence or absence of varying concentrations of JYL1421. The reduction in calcium influx is measured using fluorescence plate readers. IC50 or EC50 values are calculated from dose-response curves. Positive controls include capsazepine, a standard TRPV1 antagonist.
|
| Animal Protocol |
In vivo animal studies for TRPV1 antagonists typically use rat models. For nocifensive behavior, capsaicin is administered topically to the eye, and wiping movements are counted over a defined period. JYL1421 is administered intraperitoneally or orally prior to capsaicin challenge. For cardiovascular effects, rats are anesthetized, and blood pressure and heart rate are monitored following capsaicin injection. JYL1421 is administered at various doses (e.g., 0.4-2 mg/kg) to assess its ability to block capsaicin-induced hypotension.
|
| ADME/Pharmacokinetics |
JYL1421 is a small-molecule TRPV1 antagonist with good bioavailability following systemic administration. In vivo PK studies in rats would typically assess parameters such as half-life, Cmax, Tmax, AUC, and clearance following intravenous and oral administration. The compound is expected to distribute to tissues expressing TRPV1, including sensory neurons and the central nervous system. Detailed PK parameters are not extensively published but are consistent with those of lipophilic small-molecule antagonists.
|
| Toxicity/Toxicokinetics |
Toxicity studies of JYL1421 in preclinical models indicate that it is generally well-tolerated at pharmacologically active doses. Importantly, unlike several other TRPV1 antagonists, JYL1421 does not induce hyperthermia in rats when administered at doses ranging from 1.02 to 32.77 μmol/kg. This is a significant advantage as hyperthermia is a common on-target side effect of TRPV1 antagonists. Standard toxicity assessments would include acute and repeated-dose studies in rodents.
|
| References | |
| Additional Infomation |
JYL1421 is a selective TRPV1 receptor antagonist widely used as a research tool in pain and sensory neuroscience. It exhibits greater potency than capsazepine, a standard TRPV1 antagonist. The compound is available for research use only and is not approved for therapeutic applications. Its unique property of not inducing hyperthermia makes it a valuable tool for studying TRPV1 physiology without the confounding effects of temperature dysregulation.
|
| Molecular Formula |
C20H26FN3O2S2
|
|---|---|
| Molecular Weight |
423.57
|
| Exact Mass |
423.145
|
| CAS # |
401907-26-4
|
| PubChem CID |
10295883
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
546.6±60.0 °C at 760 mmHg
|
| Flash Point |
284.4±32.9 °C
|
| Vapour Pressure |
0.0±1.5 mmHg at 25°C
|
| Index of Refraction |
1.609
|
| LogP |
3.27
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
28
|
| Complexity |
608
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
DUHBVFMCIJLUJX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H26FN3O2S2/c1-20(2,3)16-8-5-14(6-9-16)12-22-19(27)23-13-15-7-10-18(17(21)11-15)24-28(4,25)26/h5-11,24H,12-13H2,1-4H3,(H2,22,23,27)
|
| Chemical Name |
1-[(4-tert-butylphenyl)methyl]-3-[[3-fluoro-4-(methanesulfonamido)phenyl]methyl]thiourea
|
| Synonyms |
JYL-1421; JYL 1421; JYL1421
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~236.09 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 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), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3609 mL | 11.8044 mL | 23.6088 mL | |
| 5 mM | 0.4722 mL | 2.3609 mL | 4.7218 mL | |
| 10 mM | 0.2361 mL | 1.1804 mL | 2.3609 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
