Date published: 2025-9-14

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AIF Activators

AIF activators are an eclectic group of chemical compounds that influence AIF or its associated pathways to encourage its activation. These compounds, while not directly interacting with AIF, act to disrupt mitochondrial integrity, promote oxidative stress, or induce DNA damage, thereby setting the stage for AIF release from the mitochondria. Chemicals such as Staurosporine and Resveratrol disturb mitochondrial membrane permeability, allowing AIF to translocate into the nucleus. Other compounds like N-acetylcysteine work by modulating the cellular redox status, which in turn impacts the conditions under which AIF can be activated. Yet another group, including Etoposide and Actinomycin D, act by causing DNA damage, which results in mitochondrial dysfunction and subsequently AIF activation.

Chemicals like Rotenone and Ceramide directly engage with the mitochondrial processes to activate AIF. Rotenone inhibits complex I of the electron transport chain, causing oxidative stress and leading to the release of AIF. Ceramide induces mitochondrial dysfunction by affecting mitochondrial membrane properties. In a similar vein, Bortezomib inhibits the proteasome, creating an environment where mitochondrial dysfunction is likely, thereby promoting the release of AIF. Sodium Arsenite and H2O2 are potent inducers of oxidative stress that also create conditions conducive to AIF activation.

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