Oligomycin A, created by Streptomyces, acts as a mitochondrial F0F1-ATPase inhibitor, with a Ki of 1 μM; Oligomycin A shows anti-fungal activity.
3’-Acetate-ATP, an ATP analogue, is ATP acetylation product with an maxima uv absorption at 259 nm in water at neutral pH. 3’-Acetate-ATP exerts a blocking effect on nucleic acid polymerization[1].
ATP synthase inhibitor 1 is a potent inhibitor of c subunit of the F1/FO-ATP synthase complex, inhibits mitochondrial permeability transition pore (mPTP) opening, does not affect ATP levels[1].
Apoptolidin is a polyketide isolated from Nocardiopsis bacteria[1]. Apoptolidin is a selective mitochondrial F1FO 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[1][2].
Oligomycins are macrolides created by Streptomyces species that can be toxic to other organisms through their ability to inhibit mitochondrial membrane-bound ATP synthases. The mitochondrial F1FO ATP synthase can switch to an ATP hydrolase during ischemia, so that, under these conditions, inhibition by oligomycins will reduce ATP depletion rather than block ATP synthesis.
ZW290 is a compound to activate brown adipose tissue (BAT) thermogenic function. ZW290 increases the expression of uncoupling Protein 1 (UCP1) protein and inhibits ATP synthesis in BAT[1].
Abyssinone V is a prenylated flavonoid with predicted anti-viral activity. Abyssinone V can be isolated from the stem bark of Erythrina melanacantha. Abyssinone V possesses good pharmacodynamics properties. Abyssinone V is predicted to be antivirals including anti-herpes (HSV) agent, with mechanisms comprising inhibition of polymerase, ATPase and membrane integrity[1][2].
Oligomycin B is an antibiotic isolated from marine Streptomyces, used as an eukaryotic ATP synthase inhibitor, induces apoptosis[1][2].
D-α-Hydroxyglutaric acid ((R)-2-Hydroxypentanedioic acid) 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 Ki 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[1][2][3][4][5].
FCPT is an ATP competitive kinesin-5 inhibitor.
Gboxin is an oxidative phosphorylation inhibitor targets glioblastoma. Gboxin inhibits the activity of F0F1 ATP synthase[1]. Antitumour activity[1].
Triciribine phosphate (TCN-P) inhibits amidophosphoribosyltransferase by an allosteric mechanism which affects the first committed step of de novo purine biosynthesis. Triciribine phosphate also inhibits IMP dehydrogenase which is the first committed step of guanosine nucleotide synthesis. Tricilibine phosphate does not affect ligase activity[1].
BTB06584 is an IF1-dependent selective inhibitor of the mitochondrial F1Fo-ATPase.Target: ATPasein vitro: BTB06584 inhibits F1Fo-ATPase activity with no effect on ΔΨm or O2 consumption. ATP consumption was decreased following inhibition of respiration, and ischaemic cell death was reduced. BTB06584 efficiency was increased by IF1 overexpression and reduced by silencing the protein. BTB06584 may represent a valuable tool to selectively inhibit mitochondrial F1Fo-ATPase activity without compromising ATP synthesis and to limit ischaemia-induced injury caused by reversal of the mitochondrial F1Fo-ATPsynthase.in vivo: BTB06584 rescues defective haemoglobin synthesis in zebrafish pinotage (pnt) mutants in which expression of the Atpif1a gene is lost.
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[1].
Venturicidin B (Aabomycin A2) is a macrolide antibiotic isolated from Streptomyces sp., used as an antifungal agent, a potent inhibitor of the mitochondrial F0-ATP synthase complex[1].
Mtb ATP synthase-IN-1 (compound 6ab) is a potent Mycobacterium tuberculosis (Mtb) ATP synthase inhibitor, with MIC of 0.452-0.499 μg/mL against Mtb. Mtb ATP synthase-IN-1 has good metabolic stability, low cytotoxicity (Vero IC50 > 64 μg/mL), and acceptable oral bioavailability. Mtb ATP synthase-IN-1 can be used for researching anti-mycobacterium[1].
Bongkrekic acid is a mitochondrial toxin secreted by the bacteria Pseudomonas cocovenenans[1]. 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[2].
Radicicol is an inhibitor of the ATPase/kinase with IC50 values of 1 μM, 100 μM and 400 μM, respectively for Hsp90, Topo VI and PDK3 [1]. Radicicol inhibits a wide variety of tumor cell lines by targeting Hsp90, binds to the ATPase domain of Hsp90 and prevents maturation of Hsp90 clients, leading to proteasomal degradation [2]. Radicicol is an antifungal antibiotic with antimalarial activity, impairs mitochondrial replication by targeting P. falciparum topoisomerase VIB[2]. Radicicol is an inhibitor of fat mass and obesity-associated protein (FTO), exhibits a dose-dependent inhibition of FTO demethylation activity with an IC50 value of 16.04 µM[3].