| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
TRPV4 agonist-1 targets transient receptor potential vanilloid 4 (TRPV4) with an EC₅₀ value of 1.8 μM in calcium influx assay [1]
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|---|---|
| ln Vitro |
TRPV4 agonist-1 (compound 36) demonstrated noticeably higher potency (ECmax: 20 nM in SOX9 reporter assay). TRPV1 channels are not occupied by TRPV4 agonist-1 [1].
Treatment of primary rat articular chondrocytes with TRPV4 agonist-1 (1–10 μM) dose-dependently increased the mRNA expression of chondrogenic markers COL2A1, SOX9, and ACAN, while decreasing the expression of catabolic marker MMP13 [1] - At 5 μM concentration, TRPV4 agonist-1 significantly enhanced collagen type II protein synthesis in chondrocytes as detected by Western blot [1] - TRPV4 agonist-1 (10 μM) inhibited IL-1β-induced NF-κB activation in chondrocytes, as evidenced by reduced phosphorylation of IκBα and p65 [1] |
| ln Vivo |
In surgically induced rat osteoarthritis (OA) model (anterior cruciate ligament transection + medial meniscectomy), intra-articular injection of TRPV4 agonist-1 (10 μg/joint, once weekly for 4 weeks) significantly reduced cartilage erosion and Osteoarthritis Research Society International (OARSI) score compared to vehicle control [1]
- TRPV4 agonist-1 treatment decreased synovial inflammation in OA rats, as shown by reduced levels of TNF-α and IL-6 in synovial fluid [1] - The drug preserved the thickness of articular cartilage and reduced subchondral bone sclerosis in OA rats, as demonstrated by micro-CT and histological staining [1] |
| Enzyme Assay |
Calcium influx assay: Chondrocytes were loaded with a calcium-sensitive fluorescent dye and incubated with serial dilutions of TRPV4 agonist-1. Fluorescence intensity was measured in real-time to determine the EC₅₀ value reflecting TRPV4 activation [1]
- NF-κB luciferase assay: Chondrocytes transfected with NF-κB luciferase reporter plasmid were pretreated with TRPV4 agonist-1 followed by IL-1β stimulation. Luciferase activity was measured to evaluate NF-κB inhibition [1] |
| Cell Assay |
Primary rat articular chondrocyte isolation: Articular cartilage was harvested from rat knee joints, digested with collagenase, and cultured in chondrogenic medium. Cells at passage 2 were used for experiments [1]
- mRNA expression analysis: Chondrocytes were treated with TRPV4 agonist-1 for 48 hours, total RNA was extracted, reverse-transcribed to cDNA, and qPCR was performed to detect COL2A1, SOX9, ACAN, and MMP13 mRNA levels [1] - Western blot analysis: Chondrocytes treated with the drug were lysed, proteins were separated by SDS-PAGE, transferred to membranes, and probed with antibodies against collagen type II, phospho-IκBα, and phospho-p65. Band intensity was quantified by densitometry [1] |
| Animal Protocol |
OA model establishment: Male Sprague-Dawley rats (200–250 g) underwent anterior cruciate ligament transection and medial meniscectomy under anesthesia to induce OA [1]
- Drug formulation: TRPV4 agonist-1 was dissolved in dimethyl sulfoxide (DMSO) and further diluted with phosphate-buffered saline (PBS) to a final DMSO concentration of ≤5% [1] - Administration protocol: Rats were randomly divided into vehicle control and drug-treated groups. TRPV4 agonist-1 was administered via intra-articular injection at a dose of 10 μg/joint once weekly for 4 weeks, starting 1 week after surgery [1] - Sample collection: At the end of treatment, rats were euthanized, knee joints were harvested for histological analysis and micro-CT scanning, and synovial fluid was collected for cytokine detection [1] |
| Toxicity/Toxicokinetics |
In vitro toxicity: CCK-8 assays showed that TRPV4 agonist-1 at concentrations up to 20 μM had no significant cytotoxicity to primary chondrocytes [1]
- In vivo toxicity: No significant systemic toxicity (such as weight loss, behavioral abnormalities, or organ damage) was observed in OA rats treated with TRPV4 agonist-1 during the 4-week study period [1] |
| References | |
| Additional Infomation |
TRPV4 agonist-1 is a quinazolin-4(3H)-one derivative designed as a selective TRPV4 agonist [1]. This drug exerts chondrogenic effects by activating TRPV4, thereby promoting chondrocyte differentiation and inhibiting chondrocyte catabolism and inflammatory responses [1]. In vivo studies have shown that TRPV4 agonist-1 has potential value in the treatment of osteoarthritis [1].
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| Molecular Formula |
C25H22F2N4O2
|
|---|---|
| Molecular Weight |
448.464592456818
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| Exact Mass |
448.171
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| CAS # |
2314467-59-7
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| PubChem CID |
137628676
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| Appearance |
White to off-white solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
|
| Complexity |
713
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1=CC=CC2=C1N=C(N(C1C=CC(=CC=1)OC1C=CC(=CC=1)F)C2=O)N1CCN(C)CC1
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| InChi Key |
NUGPMKZYSBKNPU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H22F2N4O2/c1-29-13-15-30(16-14-29)25-28-23-21(3-2-4-22(23)27)24(32)31(25)18-7-11-20(12-8-18)33-19-9-5-17(26)6-10-19/h2-12H,13-16H2,1H3
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| Chemical Name |
8-fluoro-3-[4-(4-fluorophenoxy)phenyl]-2-(4-methylpiperazin-1-yl)quinazolin-4-one
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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 : ~83.33 mg/mL (~185.81 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.64 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 | 2.2299 mL | 11.1493 mL | 22.2985 mL | |
| 5 mM | 0.4460 mL | 2.2299 mL | 4.4597 mL | |
| 10 mM | 0.2230 mL | 1.1149 mL | 2.2299 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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