| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
hKCNK13 41 nM (IC50) mKCNK13 28 nM (IC50) hKCNK6 >30000 nM (IC50) hKCNK2 >30000 nM (IC50)
CVN293 targets KCNK13 (potassium two‑pore domain channel subfamily K member 13, also known as THIK‑1, TASK‑1, or K2P13.1). KCNK13 is a two‑pore domain potassium (K2P) channel that is highly expressed in microglia, the resident immune cells of the central nervous system. K2P channels regulate the resting membrane potential and cellular excitability. In microglia, KCNK13 activity is linked to the activation of the NLRP3 inflammasome and the production of the pro‑inflammatory cytokine IL‑1beta. By inhibiting KCNK13, CVN293 reduces K+ efflux, thereby inhibiting NLRP3 inflammasome activation and IL‑1beta release. |
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| ln Vitro |
CVN293 (0.05, 0.5, 5 μM) has a concentration-dependent inhibitory effect on NLRP3 inflammasome-mediated LPS-induced IL-1β production in mouse microglia [1].
CVN293 is a selective and brain‑permeable potassium (K+) ion channel KCNK13 inhibitor with IC₅0 values of 41 nM and 28 nM for hKCNK13 and mKCNK13, respectively. It effectively inhibits the production of the pro‑inflammatory cytokine IL‑1beta in microglia. CVN293 (0.05, 0.5, 5 microM) has a concentration‑dependent inhibitory effect on NLRP3 inflammasome‑mediated LPS‑induced IL‑1beta production in mouse microglia. The compound is brain‑permeable, allowing it to cross the blood‑brain barrier (BBB) and target microglia in the central nervous system. |
| ln Vivo |
Pharmacokinetic Parameters of CVN293 in male Sprague-Dawley rat, dog and cynomolgus monkey[1]. IV (0.5 mg/kg; rat) PO (3 mg/kg; rat) IV (1 mg/kg; dog) PO (10 mg /kg; dog) IV (1 mg/kg; cynomolgus monkey) PO (3 mg/kg; cynomolgus monkey) Tmax (h) 1.0 1.25 1.0 Cmax (ng/mL) 468 241 165 AUC0-∞ (ng·h/mL ) 222 1236 438 630 782 546 t1/2 (h) 1.0 2.0 0.5 2.6 1.1 1.9 CLp (mL/min/kg) 35 38 22 Vss (L/kg) 1.85 1.42 1.45 F (%) 87 41 24
No specific in vivo activity data for CVN293 are reported in the search results. As a selective and brain‑permeable KCNK13 inhibitor, it has potential for evaluation in animal models of neuroinflammatory diseases, such as Alzheimer‘s disease, Parkinson‘s disease, multiple sclerosis, traumatic brain injury, and stroke. The compound could be administered orally or intraperitoneally, and endpoints would include IL‑1beta production, microglial activation, and disease severity. No specific in vivo data are provided. |
| Enzyme Assay |
The binding of CVN293 to KCNK13 is measured by standard in vitro electrophysiological assays (patch‑clamp) using cells expressing recombinant human or mouse KCNK13 channels. The compound is applied at various concentrations (0.1‑1000 nM), and the inhibition of K+ current is measured. The IC₅0 values of 41 nM (hKCNK13) and 28 nM (mKCNK13) are calculated from dose‑response curves. Alternatively, thallium (Tl+) flux assays can be used to measure KCNK13 activity in high‑throughput screening. No specific binding affinity (KD) is reported.
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| Cell Assay |
For cellular assays, mouse primary microglia or microglial cell lines (e.g., BV‑2, HMC3) are seeded in 96‑well plates. Cells are pre‑treated with CVN293 at concentrations of 0.05, 0.5, and 5 microM for 30‑60 min, then stimulated with LPS (1 microg/mL) for 6‑24 h. The production of IL‑1beta in the culture supernatant is measured by ELISA. For NLRP3 inflammasome activation, cells are primed with LPS (1 microg/mL, 4 h) and then treated with ATP (5 mM, 30 min) to activate the inflammasome. IL‑1beta release is measured by ELISA. The activation of caspase‑1 is assessed by Western blot for cleaved caspase‑1 (p20). Cell viability is assessed by MTT or LDH assays.
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| Animal Protocol |
No animal experiments for CVN293 are described in the search results. For in vivo evaluation of neuroinflammation, 6‑8‑week‑old male C57BL/6 mice would be used in a model of neuroinflammation, such as LPS‑induced neuroinflammation (intracerebroventricular (ICV) or intraperitoneal (IP) injection of LPS), or in a transgenic model of Alzheimer‘s disease (e.g., 5xFAD, APP/PS1). CVN293 would be administered orally or intraperitoneally at doses of 1‑30 mg/kg daily for 7‑14 days. Brain tissues (cortex, hippocampus) would be harvested for measurement of IL‑1beta and other cytokines (TNF‑alpha, IL‑6) by ELISA. Microglial activation would be assessed by immunofluorescence for Iba‑1 and CD68. NLRP3 inflammasome activation would be assessed by Western blot for NLRP3, ASC, and cleaved caspase‑1. No such data are provided.
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| ADME/Pharmacokinetics |
CVN293 (C14H10FN₇O, MW = 311.27, purity ≥98%, CAS 2815296-08-1) is a solid powder. For storage, the powder should be kept at -20 degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (10‑50 mM) can be prepared and stored at -80 degC for up to 6 months or at -20 degC for 1 month. For in vivo use, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween‑80 / 45% saline. No detailed PK parameters are reported, but the compound is described as brain‑permeable.
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| Toxicity/Toxicokinetics |
No specific toxicity data for CVN293 are reported. As a research‑grade KCNK13 inhibitor, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. Potassium channel inhibitors can have effects on neuronal excitability and heart function, but KCNK13 is primarily expressed in microglia, and its inhibition is expected to have a more targeted effect on neuroinflammation. No LD₅0 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
CVN293 is a research‑grade, selective, brain‑permeable inhibitor of the potassium channel KCNK13 (THIK‑1). The NLRP3 inflammasome is a multiprotein complex that plays a central role in innate immunity and the pathogenesis of several neurodegenerative diseases, including Alzheimer‘s disease, Parkinson‘s disease, multiple sclerosis, and stroke. Activation of the NLRP3 inflammasome leads to the activation of caspase‑1 and the maturation and release of the pro‑inflammatory cytokines IL‑1beta and IL‑18. Microglial KCNK13 has been identified as a key regulator of the NLRP3 inflammasome, and its inhibition represents a novel therapeutic strategy for neuroinflammatory diseases. CVN293 was discovered by researchers at the University of Texas Southwestern Medical Center. The compound has been shown to reduce IL‑1beta production in microglia and has potential for the treatment of neuroinflammatory conditions. The compound is for research use only and has not received regulatory approval.
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| Molecular Formula |
C14H10FN7O
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|---|---|
| Molecular Weight |
311.27
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| CAS # |
2815296-08-1
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| Appearance |
Solid powder
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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 : 5 mg/mL (16.06 mM; with sonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2126 mL | 16.0632 mL | 32.1264 mL | |
| 5 mM | 0.6425 mL | 3.2126 mL | 6.4253 mL | |
| 10 mM | 0.3213 mL | 1.6063 mL | 3.2126 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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