Home>>Signaling Pathways>> Proteases>> Caspase>>VX-765

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.

VX-765 Chemical Structure

Cas No.: 273404-37-8

Size Price Stock Qty
5mg
$48.00
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10mM (in 1mL DMSO)
$66.00
In stock
10mg
$77.00
In stock
50mg
$178.00
In stock
100mg
$320.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 3 publications

Product Documents

Quality Control & SDS

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Protocol

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.

Background

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.

Chemical Properties

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.

Complete Stock Solution Preparation Table

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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
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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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