2. Signaling Pathways
  3. Membrane Transporter/Ion Channel
  4. VDAC
  5. VDAC2 Isoform

VDAC2

VDAC2 encodes a mitochondrial outer-membrane voltage-dependent anion channel and supports isoform-specific regulation of mitochondrial structure, metabolite exchange, and cell-death signaling[1]. Mechanistically, VDAC2 binds BAK and restrains BAK activation, thereby limiting mitochondrial apoptosis in viable cells[2]. In tBID-triggered apoptosis, however, VDAC2 recruits BAK to mitochondria, and defined VDAC2 motifs are required for BAK import and tBID-induced mitochondrial apoptosis[3][4]. VDAC2 also enables efficient BAX-mediated apoptosis and limits tumor development, distinguishing BAX regulation from BAK regulation at the mitochondrial outer membrane[5]. In ferroptosis models, Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma, while VDAC2 and VDAC3 together facilitate erastin-induced ferroptotic cell death[6]. In tumor-immunity models, VDAC2 loss sensitizes tumor cells to IFNγ-induced mitochondrial DNA release, cGAS-STING activation, tumor destruction, and inflammatory remodeling[7]. Compared with related isoforms, VDAC2 shows a distinct apoptosis role: it is required for efficient BAX-mediated apoptosis but inhibits BAK-mediated apoptosis[5]. For experimental applications, WEHI-9625 binds VDAC2 and stabilizes the BAK-VDAC2 interaction to block mouse BAK-driven apoptosis[8].

VDAC2 Related Products (4):

Cat. No. Product Name Effect Purity
  • HY-15763
    Erastin
    		Inhibitor 99.91%
    Erastin is a ferroptosis inducer. Erastin exhibits the mechanism of ferroptosis induction related to ROS and iron-dependent signaling. Erastin inhibits voltage-dependent anion channels (VDAC2/VDAC3) and accelerates oxidation, leading to the accumulation of endogenous reactive oxygen species. Erastin also disrupts mitochondrial permeability transition pore (mPTP) with anti-tumor activity. Furthermore, Erastin can block the uptake of cystine mediated by SLC7A11 and also spares UMRC6-EV and -C91A cells from disulfidptosis under glucose starvation.
  • HY-128777
    WEHI-9625
    		Inhibitor 99.46%
    WEHI-9625 is a tricyclic sulfone, first-in-class inhibitor of apoptosis with an EC50 of 69 nM. WEHI-9625 binds to VDAC2 and promotes its ability to inhibit apoptosis driven by mouse BAK. WEHI-9625 is completely inactive against both human BAK and the closely related apoptosis effector BAX.
  • HY-172262
    WEHI-3773
    		Ligand 99.89%
    WEHI-3773 is a VDAC2 ligand and apoptosis modulator. WEHI-3773 directly binds to the β7-β10 region of VDAC2 and disrupts its interaction with BAX and BAK. WEHI-3773 regulates BAX-mediated apoptosis in BAK-deficient cells by modulating conformational activation of BAX, mitochondrial redistribution, and cytochrome c release. WEHI-3773 overcomes Venetoclax (HY-15531) resistance, resensitizes leukemia cells carrying BAX mutations to BH3 mimetics, and enables long-term clonogenic survival of BAK-deficient cells treated with BH3 mimetics. WEHI-3773 is applicable to research related to acute myeloid leukemia.
  • HY-181529
    NCATS-SM0225
    		Ligand
    NCATS-SM0225 is an endoplasmic reticulum-associated degradation (ERAD) inhibitor and a direct binder of VDAC1, VDAC2 and VDAC3. NCATS-SM0225 exhibits an IC50of 1.02 μM for ERAD and a Kd of 3.13 μM for human VDAC1 binding. NCATS-SM0225 disrupts cellular calcium homeostasis, enhances VDAC1-IP3R coupling and activating PERK. NCATS-SM0225 selectively kills cancer cells, exhibits tumor growth inhibitory effects in melanoma xenograft models. NCATS-SM0225 can be used for research on multiple cancers including melanoma, as well as the molecular mechanisms of ERAD and calcium homeostasis regulation.