Chemicals classified as SPATA18 inhibitors based on the information above are compounds that can modulate mitochondrial function and autophagy pathways, which are processes closely related to the biological role of SPATA18. These chemicals, although not directly targeting SPATA18, can indirectly affect its activity by altering the cellular environment or the pathways in which SPATA18 is involved. Oligomycin and Antimycin A are well-known inhibitors of mitochondrial respiration, targeting ATP synthase and complex III, respectively. These compounds can lead to mitochondrial dysfunction, which is likely to have a downstream effect on mitophagy and potentially the function of SPATA18. FCCP is a mitochondrial uncoupler that dissipates the proton gradient across the mitochondrial membrane, which can also trigger mitophagic processes that SPATA18 may be part of.
Mdivi-1, Nicotinamide, and Rotenone affect various aspects of mitochondrial dynamics and function. Mdivi-1 can inhibit mitochondrial fission, which is a crucial step in the sequestration of damaged mitochondria during mitophagy. Nicotinamide is a precursor to NAD+, a crucial molecule in cellular metabolism that influences mitochondrial turnover and health. Rotenone, by inhibiting complex I, can cause mitochondrial stress that may instigate mitochondrial quality control mechanisms involving SPATA18. Chloroquine and 3-MA are recognized autophagy inhibitors. Chloroquine prevents the fusion of autophagosomes with lysosomes, and 3-MA inhibits autophagy at an early stage by targeting class III PI3K. Bafilomycin A1 disrupts autophagosome maturation by inhibiting V-ATPase. By blocking autophagy, these compounds can alter the cellular processes in which SPATA18 participates. Rapamycin is a well-known inducer of autophagy through mTOR inhibition and is widely used to study autophagic processes. Metformin activates AMPK, leading to the induction of mitophagy, while Resveratrol promotes mitophagy through SIRT1 activation
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