VBIT-4 inhibits the oligomerization of voltage-dependent anion channel 1 (VDAC1) with a binding affinity (Kd) of 17 μM. As an inhibitor of apoptosis, it has potential therapeutic applications in conditions associated with apoptosis, including neurodegenerative and cardiovascular diseases [1].
体外研究
VBIT-4 acts on the mitochondrial protein VDAC1 to prevent apoptosis and safeguard against mitochondrial dysfunction. At concentrations of 0.1-10 μM, VBIT-4 (0.1-10 μM) blocks VDAC1 oligomerization, Cyto-C release from mitochondria, and apoptosis in HEK-293 cells, with IC50 values of 1.9±0.08 μM, 1.8±0.24 μM, and 2.9±0.12 μM, respectively [1].
VBIT 4 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HeLa cells
10 µM
1 hour
VBIT-4 suppressed the release of mtDNA caused by Phb1 knockdown
EMBO J. 2022 Dec 15;41(24):e111173.
J774A.1 cells
10 µM
1 hour
VBIT-4 suppressed the release of mtDNA caused by Phb1 knockdown
EMBO J. 2022 Dec 15;41(24):e111173.
NSC-34 cells
15 µM
12 hours
VBIT-12 partially prevented the mutant SOD1-induced cell toxicity
Int J Mol Sci. 2022 Sep 1;23(17):9946.
Mouse lung endothelial cells
5 µM
36 hours
VBIT-4 prevented hyperglycemia-induced cell death and mitochondrial dysfunction, inhibiting spontaneous MPT pore opening and ROS generation.
Antioxidants (Basel). 2023 Jul 20;12(7):1459.
Rat cortical neurons
10 µM
6, 24, 48 hours
VBIT-4 prevented Aβ-induced VDAC1 overexpression and apoptotic cell death
Transl Neurodegener. 2022 Dec 28;11(1):58.
Endog−/− MEFs
10 µM
VBIT-4 decreased cmtDNA levels and ISG expression
Science. 2019 Dec 20;366(6472):1531-1536.
MDA231
10 µM
VBIT-4 induces VDAC1 monomerization and promotes PRKN-mediated polyubiquitination
Autophagy. 2023 Sep;19(9):2443-2463.
MDA468
10 µM
VBIT-4 induces VDAC1 monomerization and promotes PRKN-mediated polyubiquitination
Autophagy. 2023 Sep;19(9):2443-2463.
VBIT 4 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
MpJ- Faslpr lupus-prone mice
10 μM
VBIT-4 ameliorated lupus-like symptoms, including the reduction of skin lesions, renal immune complex deposition, proteinuria, anti-dsDNA antibody, antinuclear antibody, IgG, and cell-free mtDNA levels
Science. 2019 Dec 20;366(6472):1531-1536.
Mice
5 × FAD mouse model
Drinking water
20 mg/kg
Twice a week for 5 months
VBIT-4 prevented cognitive decline, neuronal loss, neuroinflammation, and neuro-metabolic dysfunctions
Transl Neurodegener. 2022 Dec 28;11(1):58.
C57BL/6 mice
DSS-induced colitis model
Drinking water
20 mg/kg
From day 2 or day 5 until day 14
VBIT-12 significantly alleviated DSS-induced colitis pathology, inhibited inflammatory cell infiltration, apoptosis, mtDNA release, and NLRP3 inflammasome activation, and reduced the inflammatory response
Mol Ther. 2022 Feb 2;30(2):726-744
Mice
SOD1G93A mutant mice
Intraperitoneal injection
26 mg/kg
Every other day for 12 weeks
VBIT-12 significantly improved muscle endurance in SOD1G93A mutant mice
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