ATP Synthase Inhibitor

Oligomycin, an antifungal antibiotic, is an inhibitor of H⁺-ATP-synthase. Oligomycin blocks oxidative phosphorylation and the electron transport chain. Oligomycin inhibits HIF-1alpha expression in hypoxic tumor cells.

Oligomycin A (MCH 32), created by Streptomyces, acts as a mitochondrial F₀F₁-ATPase inhibitor, with a K_i of 1 μM; Oligomycin A shows anti-fungal activity.

D-α-Hydroxyglutaric acid disodium (Disodium (R)-2-hydroxyglutarate) is the principal metabolite accumulating in neurometabolic disease D-2-hydroxyglutaric aciduria. D-α-Hydroxyglutaric acid disodium is a weak competitive antagonist of α-ketoglutarate (α-KG) and inhibits multiple α-KG-dependent dioxygenases with a K_i of 10.87 mM. D-α-Hydroxyglutaric acid disodium increases reactive oxygen species (ROS) production. D-α-Hydroxyglutaric acid disodium binds and inhibits ATP synthase and inhibits mTOR signaling.

Bongkrekic acid is a mitochondrial toxin secreted by the bacteria Pseudomonas cocovenenans. Bongkrekic acid specific ligand for mitochondrial adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid has to cross the mitochondrial inner membrane to produce its inhibitory effect on ADP/ATP transport.

Gboxin is an oxidative phosphorylation (OXPHOS) inhibitor that targets glioblastoma. Gboxin inhibits the activity of F₀F₁ ATP synthase. Antitumour activity.

YHV98-4 is a selective, blood-brain barrier permeable Hv1 channel inhibitor. YHV98-4 specifically inhibits Hv1 with a half-maximal inhibitory concentration of 1 µM without inhibiting other ion channels. YHV98-4 reduces the propagation of p-tau. YHV98-4 increases ATP production, and enhances microglial mitophagy. YHV98-4 attenuates inflammatory pain via inhibition of Hv1 and ROS production. YHV98-4 enhances microglia-to-neuron mitochondrial transfer, promoting the delivery of functional mitochondria to rescue neuronal damage and improve cognitive function. YHV98-4 reduces inflammation. YHV98-4 can be used in the research of Alzheimer's disease.

ND-011458 is an Antibacterial agent, a QcrB inhibitor, and also an inhibitor of cytochrome bcc:aa3 oxidase function. ND-011458 binds to the QcrB subunit of cytochrome bcc:aa3 oxidase. ND-011458 inhibits ATP formation. When used in combination with Clofazimine (HY-B1046), ND-011458 exhibits bactericidal activity against Mycobacterium abscessus. ND-011458 can be used in studies related to Mycobacterium abscessus pulmonary infections.

D-α-Hydroxyglutaric acid ((R)-2-Hydroxyglutarate) is the principal metabolite accumulating in neurometabolic disease D-2-hydroxyglutaric aciduria. D-α-Hydroxyglutaric acid is a weak competitive antagonist of α-ketoglutarate (α-KG) and inhibits multiple α-KG-dependent dioxygenases with a K_i of 10.87 mM. D-α-Hydroxyglutaric acid increases reactive oxygen species (ROS) production. D-α-Hydroxyglutaric acid binds and inhibits ATP synthase and inhibits mTOR signaling.

Formic acid ammonium is the ammonium salt form of formic acid, which is an endogenous metabolite. Formic acid ammonium activates the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway in endothelial cells and inhibits calcium ion influx in vascular smooth muscle cells, resulting in vasomotor relaxation. Formic acid ammonium inhibits cytochrome C oxidase (CcO) and disrupts the electron transport chain, leading to ATP depletion. Formic acid ammonium can be used as a feed additive, which can lower the feed pH value, inhibit the growth of microorganisms (such as Escherichia coli, Salmonella), and extend the shelf life of the feed.

3-Hydroxyisobutyric acid is an intermediate in the metabolic pathways of L-valine and thymine, and can be found in urine. 3-Hydroxyisobutyric acid is a secreted mediator of endothelial cell fatty acid transport and insulin resistance. 3-Hydroxyisobutyric acid can also inhibit key enzymes of energy metabolism in the cerebral cortex of young rats. The levels of 3-Hydroxyisobutyric acid are closely related to various diseases such as 3-hydroxyisobutyric aciduria, diabetes, and ketoacidosis.

IR-783 (ADS 780WS) is a heptamethine cyanine dye. IR-783 induces Mitochondrial membrane potential loss, ATP depletion, mitochondrial permeability transition pore opening, Cytochrome c release and Apoptosis in breast cancer cells. IR-783 promotes the translocation of Drp1 from the cytosol to mitochondria. IR-783 increases the expression of mitochondrial fission proteins such as MFF and Fission-1. IR-783 possesses imaging, cancer-targeting and anticancer properties. IR-783 exerts anticancer effects against breast cancer. IR-783 can be used in breast cancer-related research.

KM91104 is a cell-permeable V-ATPase a3-b2 inhibitor (IC₅₀ = 2.3 µM). KM91104 reduces the metabolic activity, cell proliferation capacity and V-ATPase subunit protein expression levels of primary human hepatic stellate cells, increases intracellular ATP levels and decreases cytoplasmic pH. KM91104 reduces TLR4 expression on the surface of oligodendrocyte precursor cells, blocks the ENV-TLR4 interaction, and reverses oligodendrocyte myelination defects induced by ENV protein.

BTB06584 is a selective and IF1-dependent mitochondrial F₁F_o-ATPase inhibitor without compromising ATP synthesis. BTB06584 can delays ischaemic cell death.

MS-L6 is a OXPHOS inhibitor and antimalarial agent. MS-L6 inhibits NADH oxidation and electron transport. MS-L6 induces OXPHOS uncoupling, dissipates mitochondrial membrane potential, increases non-ATP-coupled oxygen consumption, and reduces ATP synthesis. MS-L6 triggers the production of ROS. MS-L6 exhibits anti-amoebic activity. MS-L6 exerts antitumor activity in mouse lymphoma xenograft models. MS-L6 can be used in research related to B-cell lymphoma, T-cell lymphoma, and non-Hodgkin B-cell lymphoma.

Oligomycin B is an antibiotic that acts as a non-selective inhibitor of ATP Synthase. Oligomycin B increases mitochondrial membrane potential. Oligomycin B induces apoptosis and necrosis. Oligomycin B impairs the motility of Plasmopara viticola zoospores and induces their lysis. Oligomycin B inhibits Magnaporthe oryzae (wheat blast fungus) and suppresses the development of wheat blast. Oligomycin B reduces hyphal growth and spore germination of Botrytis cinerea, and protects Arabidopsis thaliana against Botrytis cinerea infection. Oligomycin B exacerbates cytotoxic brain edema in rats with cerebral cortical contusion, increases intracranial pressure and brain water content, and aggravates mitochondrial damage in these rats. Oligomycin B is used in studies related to grape downy mildew, traumatic brain injury, wheat blast, and gray mold.

Venturicidin A (Aabomycin A1), from actinomycetes, is a membrane-active natural product inhibitor of ATP synthase. Venturicidin A potentiates the aminoglycoside antibiotic gentamicin against multidrug-resistant clinical isolates of Staphylococcus, Enterococcus, and Pseudomonas aeruginosa. Venturicidin A shows noticeable toxicity toward human embryonic-kidney (HEK)cells with an IC50 of 31 μg/mL.

Licoflavone B is an orally active flavonoid, with IC₅₀ values of 23.78 μM and 31.5 μM against SmATPase and SmADPase of Schistosoma mansoni, respectively. Licoflavone B selectively targets viral RdRp, inhibits viral replication, and reduces the expression levels of viral NP and PB2. Licoflavone B inhibits c-Myc expression and suppresses cancer cell proliferation. Licoflavone B disrupts the tegument of worms, reduces egg production, and induces the death of adult Schistosoma mansoni. Licoflavone B blocks the activation of the MAPK pathway, maintains colonic barrier integrity, inhibits colonic cell apoptosis, and reshapes the gut microbiota. Licoflavone B can be used in research related to influenza, multiple myeloma, schistosomiasis, and ulcerative colitis.

ATPase-IN-4 (Compound MS1) inhibits the ATPase activity of EHD4 (IC₅₀: 0.92 μM). ATPase-IN-4 also inhibits EHD2 enzymatic activity

Apoptolidin is a polyketide isolated from Nocardiopsis bacteria. Apoptolidin is a selective mitochondrial F₁F_O ATPase inhibitor. Apoptolidin is an apoptosis inducer and induces apoptotic cell death in cells transformed with the adenovirus type 12 oncogenes including ElA (IC₅₀=10-17 ng/ml) but not in normal cells.

Parimifasor (LYC-30937) is an orally active agent for inflammatory bowel disease. Parimifasor targets F1F0-ATPase. Parimifasor acts on respiratory complex V, slows ATP production and induces Apoptosis. Parimifasor can be used in the research of inflammatory bowel disease.