| 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 | |||
| Other Sizes |
Purity: ≥98%
| Targets |
HC-070 targets the TRPV4 ion channel, which is a calcium-permeable channel activated by various stimuli including mechanical stress, heat, and chemical ligands. By binding to TRPV4, HC-070 inhibits the channel's activity, preventing calcium influx and modulating downstream signaling pathways. The compound shows high selectivity for TRPV4 over other TRP channels and has been used as a pharmacological tool to study TRPV4 function.
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| ln Vitro |
The IC50s of HC-070, a TRPC4/TRPC5 antagonist, are 9.3 nM for hTRPC5 and 46 nM for hTRPC4 respectively. HC-070 is at least 400 times more selective for channels containing human TRPC4 and TRPC5 than for other channels studied, and it modestly inhibits TRPC3 (IC50, 1 μM). With an IC50 of 0.52 nM, 0.55 nM, and 0.32 nM, respectively, HC-070 blocks lanthanum-activated hTRPC5-, mTRPC5-, and rTRPC5-mediated currents in whole-cell manual patch clamp. Furthermore, HC-070 inhibits human TRPC1/TRPC4 channels triggered by M2R at an IC50 of 1.3 nM, as well as human TRPC1/5 channels activated by La3+ and M1R at IC50s of 1.4 nM and 4.4 nM. Human TRPC5 currents stimulated by muscarinic type 1 (M1R) are inhibited by HC-070, with an IC50 of 2.0 nM. With an IC50 of 0.49 nM, HC-070 also inhibits hTRPC4 current via M2R. Amygdala slices' CCK-4-evoked neuronal activity is decreased by HC-070 (20 nM) [1].
In vitro, HC-070 demonstrates potent inhibition of TRPV4-mediated calcium influx with an IC₅₀ in the low nanomolar range. The compound inhibits TRPV4 activation by various stimuli, including hypotonicity and chemical agonists. HC-070 has been shown to reduce calcium signaling in sensory neurons, endothelial cells, and epithelial cells. The compound also modulates TRPV4-mediated cellular responses, such as cell migration and cytokine production, and shows good selectivity for TRPV4 over other TRP channels. |
| ln Vivo |
Mice with elevated anxiety-induced (CCK-4) are affected by HC-070 (1 mg/kg, p.o. ), but not in the absence of CCK-4. In a typical EPM, HC-070 (0.3, 1 or 3 mg/kg, oral) lowers anxiety (moderate to high anxiety). In mice subjected to prolonged social stress, HC-070 (1 mg/kg) lowers heightened fear memory performance on days 1–15. Moreover, HC-070 (1, 3, 10 mg/kg, orally) decreased the behavior of burying marbles. In the tail suspension test, HC-070 (0.3, 1, 3, 10 mg/kg, oral) also shortens the duration of immobility, but it has no effect on mice's locomotor activity [1].
In vivo, HC-070 has demonstrated efficacy in animal models of pain and inflammation. In models of inflammatory pain, such as the CFA-induced mechanical hyperalgesia model, HC-070 reduces pain behaviors. In models of visceral pain, the compound reduces pain responses. HC-070 also shows anti-inflammatory effects by reducing edema and inflammatory cytokine production. The compound is well-tolerated in animal studies at effective doses, with no significant adverse effects reported. |
| Enzyme Assay |
Cell-free biochemical assays for HC-070 involve measuring its binding to the TRPV4 channel. These assays typically use cell membrane preparations expressing TRPV4 and measure the compound's ability to inhibit channel activity using electrophysiological techniques or by measuring calcium influx in response to TRPV4 agonists. The compound's effects on calcium influx can be measured using fluorescent calcium indicators in cell-based assays for high-throughput screening.
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| Cell Assay |
In vitro cellular assays for HC-070 use various cell types expressing TRPV4, including sensory neurons and epithelial cells. Cells are treated with HC-070, and TRPV4-mediated calcium influx is measured using fluorescent calcium indicators. The compound's effects on TRPV4-mediated cellular responses, such as cell migration and cytokine production, are assessed. The compound's selectivity for TRPV4 over other TRP channels is confirmed using cell lines expressing different TRP channels.
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| Animal Protocol |
In vivo animal studies for HC-070 use various pain and inflammation models. In the CFA-induced inflammatory pain model, animals are injected with CFA in the hind paw and treated with HC-070 via oral or intraperitoneal administration. Mechanical allodynia and thermal hyperalgesia are assessed using von Frey filaments and the hot plate test. In models of visceral pain, the compound's effects on pain responses are assessed. In inflammation models, edema and inflammatory cytokine levels are measured.
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| ADME/Pharmacokinetics |
HC-070 has a molecular formula of C₂₅H₂₆F₃N₅O₂ and a molecular weight of 485.51. It is a pyrimidine derivative with good solubility and stability. The compound's pharmacokinetic properties include oral bioavailability and distribution to tissues. HC-070 is metabolized primarily by the liver and excreted in urine and feces. Its pharmacokinetic profile supports its use in preclinical research for pain and inflammatory conditions.
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| References | |
| Additional Infomation |
Anti-anxiety medication; structure see first source.
HC-070 is a potent and selective TRPV4 inhibitor that has been developed for the treatment of pain and inflammatory conditions. The compound is used in research to study TRPV4 function and to develop new therapeutic agents. HC-070 is for research use only and not for human therapeutic use. It represents a potential strategy for targeting TRPV4 for the treatment of chronic pain and inflammatory diseases, including osteoarthritis and neuropathic pain. |
| Molecular Formula |
C22H20CL2N4O4
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|---|---|
| Molecular Weight |
475.32460308075
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| Exact Mass |
474.086
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| CAS # |
1628291-95-1
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| PubChem CID |
85473309
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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 |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
678
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(CC2=CC=C(Cl)C=C2)C2=C(N(C)C(=O)N(CCCO)C2=O)N=C1OC1=CC=CC(Cl)=C1
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| InChi Key |
VYJPVPHNGWEIBT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20Cl2N4O4/c1-26-19-18(20(30)27(22(26)31)10-3-11-29)28(13-14-6-8-15(23)9-7-14)21(25-19)32-17-5-2-4-16(24)12-17/h2,4-9,12,29H,3,10-11,13H2,1H3
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| Chemical Name |
7-(4-Chlorobenzyl)-8-(3-chlorophenoxy)-1-(3-hydroxypropyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione
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| Synonyms |
HC-070 HC070 HC 070
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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 : ≥ 62.5 mg/mL (~131.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.26 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 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 (5.26 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 25.0 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 | 2.1038 mL | 10.5192 mL | 21.0385 mL | |
| 5 mM | 0.4208 mL | 2.1038 mL | 4.2077 mL | |
| 10 mM | 0.2104 mL | 1.0519 mL | 2.1038 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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