VX-765 (Synonyms: VX-765) |
Catalog No.GC12725 |
A prodrug form of VRT-043198
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 273404-37-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment [1]: | |
Cell lines |
human umbilical mesenchymal stem cells(HUMSCs) |
Preparation Method |
MTT assay was used to test the toxicity of VX-765. Oxygen-glucose deprivation (OGD) was applied to mimic ischemic environment in vitro experiments, and The apoptosis of HUMSCs incubated with VX-765 was assessed 12 or 24 hours after OGD exposure. |
Reaction Conditions |
10µM VX-765 for 12, 24h. |
Applications |
Compared to OGD groups, TUNEL-positive cells, IL-1β, and IL-6 decreased while IL-10 increased in VX-765+OGD group. The result demonstrate the anti-apoptosis and anti- inflammatory role of VX-765 in HUMSCs. |
Animal experiment [2]: | |
Animal models |
CD1 (ICR) mice |
Preparation Method |
CD1 (ICR) mice were injected intraperitoneally with 55 mg/kg streptozotocin(STZ). Mice with blood glucose level over 300 mg/dL were considered diabetic.Diabetic mice were administered with VX-765 for 8 weeks.The treatment with VX-765 was initiated 2 weeks after STZ injection |
Dosage form |
100mg/kg VX-765, intraperitoneal(i.p.) injection |
Applications |
Administration of VX-765 in diabetic mice effectively ameliorated renal function, compared with that of untreated diabetic mice.VX-765 treatment did not affect blood glucose level or body weight, illustrating that VX-765 ameliorated diabetic nephropathy independent of its metabolic effects. |
References: [1]. Sun Z, Gu L, et al. VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway. CNS Neurosci Ther. 2020 Sep;26(9):952-961. [2]. Wen S, Deng F, et al. VX-765 ameliorates renal injury and fibrosis in diabetes by regulating caspase-1-mediated pyroptosis and inflammation. J Diabetes Investig. 2022 Jan;13(1):22-33. |
VX-765 is a newly developed, selective, small molecule caspase-1 inhibitor that can pass the blood-brain barrier and reduce inflammation in vitro and in vivo[1].
VX-765 potently and specifically inhibited human Casp1 (IC50 3.68?nM)[2]. Increases of autophagy-related proteins were detected in VX-765-pretreated human umbilical mesenchymal stem cells(HUMSCs), indicating the potential of VX-765 for up-regulating autophagy. Meanwhile, increased p-AMPK and decreased p-mTOR were detected in VX-765-pretreated HUMSCs. Furthermore, the anti-inflammatory and anti-apoptosis effect of VX-765 could be abolished by an autophagy inhibitor or AMPK inhibitor[3]
In vivo,VX-765 ameliorated renal dysfunction, tubular injury, and renal inflammation in mice with DN, but had no effect on blood glucose level or body weight, illustrating that VX-765 represents a novel and efficacious therapeutic treatment for DN without increasing the risk of hypoglycemia in diabetic patients[4]
References:
[1]. Boxer MB, Quinn AM, et al. A highly potent and selective caspase 1 inhibitor that utilizes a key 3-cyanopropanoic acid moiety. ChemMedChem. 2010 May 3;5(5):730-8.
[2]. Flores J, No?l A, et al. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model. Nat Commun. 2018 Sep 25;9(1):3916.
[3]. Sun Z, Gu L, et al. VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway. CNS Neurosci Ther. 2020 Sep;26(9):952-961.
[4]. Wen S, Deng F, et al. VX-765 ameliorates renal injury and fibrosis in diabetes by regulating caspase-1-mediated pyroptosis and inflammation. J Diabetes Investig. 2022 Jan;13(1):22-33.
Cas No. | 273404-37-8 | SDF | |
Synonyms | VX-765 | ||
Chemical Name | (2S)-1-[(2S)-2-[(4-amino-3-chlorobenzoyl)amino]-3,3-dimethylbutanoyl]-N-[(2R,3S)-2-ethoxy-5-oxooxolan-3-yl]pyrrolidine-2-carboxamide | ||
Canonical SMILES | CCOC1C(CC(=O)O1)NC(=O)C2CCCN2C(=O)C(C(C)(C)C)NC(=O)C3=CC(=C(C=C3)N)Cl | ||
Formula | C24H33ClN4O6 | M.Wt | 508.99 |
Solubility | ≥ 313 mg/mL in DMSO, ≥ 50.5 mg/mL in EtOH with ultrasonic | Storage | Desiccate at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.9647 mL | 9.8234 mL | 19.6468 mL |
5 mM | 0.3929 mL | 1.9647 mL | 3.9294 mL |
10 mM | 0.1965 mL | 0.9823 mL | 1.9647 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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