Mitochondrial Metabolism

Imeglimin hydrochloride (EMD 387008 hydrochloride) prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration.

MPP+ iodide, the metabolite of a neurotoxin MPTP, causes symptom of Parkinson's disease (PD) in animal models by selectively destroying dopaminergic neurons in substantia nigra. MPP+ induces dopamine transporter (DAT) externalization in dopaminergic (DA)

Lipoic acid (R-(+)-Thioctic acid) is an organosulfur compound derived from octanoic acid. It is made in animals normally, and is essential for aerobic metabolism.

4-methyl-6-phenyl-2H-pyranone is derived from Scutellaria baicalensis Georgi and improves mitochondrial functionality to protect astrocytes against hydrogen peroxide-induced toxicity.

TT01001 (Ethyl 4-(3-(3,5-dichlorophenyl)thioureido)piperidine-1-carboxylate) is a selective agonist of mitoNEET and reduces oxidative stress injury and neuronal apoptosis by improving mitochondrial dysfunction. TT01001 can be used in studies about the treatment of type II diabetes.

McN3716 is a carnitine palmitoyltransferase I (CPT-1) inhibitor for the study of metabolic diseases.

VK-28 is a brain permeable iron chelator with neuroprotection. VK-28 inhibits basal as well as iron-induced mitochondrial lipid peroxidation.

ND-011992 is a reversible and selective quinazoline inhibitor targeting quinone reductases and quinol oxidases.ND-011992 inhibits E. coli BL21*Δcyo respiratory complex I. ND-011992 inhibits bo3 oxidase, bd-I oxidases and bd-II oxidases, ND-011992 inhibits E. coli BL21*Δcyo respiratory complex I, bo3 oxidase, bd-I oxidases, and bd-II oxidases with IC50s of 0.12, 2.47, 0.63, and 1.3 μM, respectively.ND-011992 can be used in the study of tuberculosis.

Tebufenpyrad (Comanche) (mitochondrial complex-1 inhibitors) is an agro-chemically important acaricide that functions like the known mitochondrial toxicant rotenone.

(S)-Coriolic acid (13(S)-HODE) is an important intracellular signaling agent, generated by the reaction of linoleic acid with plant and mammalian lipoxygenases, and is involved in cell proliferation and differentiation in various biological systems. (S)-Coriolic acid inhibits the adhesion of tumor cells to the vascular endothelium and down-regulates the expression of IRGpIIb IIIa receptors at around 1 μM. (S)-Coriolic acid is a metabolite of 15-lipoxygenase (15-LOX), which often acts as an endogenous ligand to activate PPARγ. (S)-Coriolic acid induces mitochondrial dysfunction and airway epithelial damage.

Glibenclamide (Glyburide) is an antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.

Schaftoside (APIGENIN-6-GLUCOSIDE-8-ARABINOSIDE) has antioxidant and anticancer activity.

Lonidamine (Diclondazolic Acid) is an indazole carboxylic acid derivative, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK).

MSDC 0160 (CAY10415) is a prototype mTOT-modulating insulin sensitizer being used in trials studying the treatment of Type 2 Diabetes and Alzheimer's Disease.

Daidzin (Daidzoside) is an isoflavone isolated from soya bean with anti-oxidant, anti-carcinogenic, and anti-atherosclerotic activities.

(-)-Epigallocatechin Gallate (EGCG) is an antioxidant polyphenol flavonoid that inhibits telomerase and DNA methyltransferase. (-)-Epigallocatechin Gallate (EGCG) blocks the activation of EGF receptors and HER-2 receptors. (-)-Epigallocatechin Gallate (EGCG) is a phenolic antioxidant found in a number of plants such as green and black tea. It inhibits cellular oxidation and prevents free radical damage to cells.

IACS-010759 is an orally bioavailable inhibitor of complex I of oxidative phosphorylation of the mitochondrial electron transport chain.

Rotenone (Rotocide) is a natural product and a botanical insecticide. Rotenone is a mitochondrial electron transport complex I inhibitor that promotes the production of reactive oxygen species in mitochondria and induces apoptosis.

FCCP (Trifluoromethoxy carbonylcyanide phenylhydrazone) is an oxidative phosphorylation (OXPHOS) inhibitor and mitochondrial proton carrier uncoupler. FCCP is often used as an apoptosis inducer.

CCCP (Carbonyl Cyanide m-Chlorophenylhydrazone) is an oxidative phosphorylation (OXPHOS) inhibitor and mitochondrial proton carrier uncoupler. CCCP inhibits the activation of STING and its downstream signaling molecules TBK1 and IRF3.

Mito-TEMPO is a mitochondria-targeted superoxide dismutase mimetic. Mito-TEMPO scavenges superoxide and alkyl radicals and prevents mitochondrial oxidation, necrosis and apoptosis.

Speract, a peptide from sea urchin eggs, regulates sperm motility and stimulates sperm mitochondrial metabolism.

Boscalid is a broad-spectrum carboxamide fungicide that inhibits fungal respiration by binding to the ubiquinone site of mitochondrial complex II/succinate dehydrogenase.1It suppresses mycelial growth ofS. minorby 87 to 100% and ofS. sclerotiorumby 77 to 100% when used at a concentration of 1 μg/ml.2In field studies, boscalid applied at 5.6 μg/cm2provides 55.5 and 30.4% disease control for lettuce drop caused byS. minorandS. sclerotiorum, respectively. It decreases cell viability of mouse primary cortical neurons following long-term exposure but is not cytotoxic (LC50= >100 μM for acute and continuous exposure). Formulations containing boscalid have been used in agriculture to prevent fungal growth on crops. 1.Wang, Y., Duan, Y., Wang, J., et al.A new point mutation in the iron-sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorumMol. Plant Pathol.16(7)653-661(2015) 2.Matheron, M.E., and Porchas, M.Activity of boscalid, fenhexamid, fluazinam, fludioxonil, and vinclozolin on growth of Sclerotinia minor and S. sclerotiorum and development of lettuce dropPlant Dis.88(6)665-668(2004)

FGIN-1-43 is a potent and specific ligand for the mitochondrial DBI receptor.

Z16078526 enhances thermogenesis in mice by inducing endogenous Ucp1 expression, promoting p38 MAPK phosphorylation, and stimulating lipolysis in primary mouse brown adipocytes. Additionally, it activates thermogenic gene expression and mitochondrial activity, specifically uncoupled respiration, in these cells.

D-Histidine is an enantiomer of L-histidine. L-Histidine is an inhibitor of mitochondrial glutamine transport and also an essential amino acid for infants.

NDH-1 inhibitor-1 is an effective NDH-1 inhibitor, which can inhibit bovine SMP (mitochondrial granules), potato SMP and Escherichia coli, with pI50 values of <4, 5.40, 6.15 µM, respectively.

MitoSOX Red is a novel fluorescent probe that is specific and cell membrane-permeable and targets mitochondria in living cells.MitoSOX Red is oxidized by superoxide upon entry into the mitochondria and is not oxidized by other ROS or RNS-generating systems.MitoSOX Red then binds to nucleic acids in the mitochondrion and produces a strong red fluorescence.MitoSOX Red can be used as a fluorescent indicator for the specific detection of superoxide.MitoSOX Red can be used as a fluorescent indicator for the specific detection of superoxide. MitoSOX Red can be used as a fluorescent indicator to specifically detect superoxide. Superoxide dismutase (SOD) prevents the oxidation of MitoSOX Red.

SCAL-255 is a mitochondrial complex I (CI) inhibitor, exhibiting potent inhibition with an IC50 of 1.14 μM. It impedes mitochondrial function by blocking oxygen consumption rate (OCR), inducing reactive oxygen species (ROS) production, and diminishing mitochondrial membrane potential (MMP). Furthermore, SCAL-255 significantly hampers the proliferation of cancer cells reliant on oxidative phosphorylation (OXPHOS) [1].

Mitochondrial fusion promoter M1, a modulator of mitochondrial dynamics, enhances mitochondrial function and cellular respiration, and has shown efficacy in reducing brain and cardiac damage in rats suffering from cardiac ischemia/reperfusion injury.

L-2-Hydroxyglutaric acid disodium ((S)-2-Hydroxyglutaric acid disodium) is an epigenetic modifier and putative oncometabolite in renal cancer. L-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase (Mi-CK) activity(Km and Ki of 2.52 mM and 11.13 mM, respectively).

α-Lipoic Acid (DL-α-Lipoic acid) an octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.

Imeglimin (EMD 387008) is an orally available antidiabetic compound that enhances mitochondrial function, enhances insulin secretion, promotes β-cell proliferation and improves pancreatic β-cell survival in mice.

THP104c is an inhibitor of mitochondrial fission.

Tricarballylic acid (Carballylic acid) is an inhibitor of aconitase.

GW604714X (2,4-Thiazolidinedione, 5-[[5-[6-(4-acetyl-1-piperazinyl)-3-nitro-2-pyridinyl]-2-fluorophenyl]methylene]-) were found to be potent inhibitors of mitochondrial respiration supported by pyruvate

CTPI-2 is an inhibitor of mitochondrial citrate carrier SLC25A1 with(KD : 3.5 μM). CTPI-2 inhibits glycolysis, PPARγ, and its downstream target the glucose transporter GLUT4. CTPI-2 exhibits anti-tumor activity.CTPI-2 halts salient alterations of NASH reverting steatosis, preventing the evolution to steatohepatitis, reducing inflammatory macrophage infiltration in the liver and adipose tissue, and starkly mitigating obesity induced by a high-fat diet.

Nerol (Neryl alcohol) is a monoterpene found in many essential oils, such as lemon balm and hop.Nerol can lessened the severity of ouabain-triggered arrhythmias in mammalian heart.

L-Histidine (L-(-)-Histidine) is a semi-essential amino acid (children should obtain it from food) needed in humans for growth and tissue repair, L-Histidine is important for maintenance of myelin sheaths that protect nerve cells and is metabolized to the neurotransmitter histamine. Histamines play many roles in immunity, gastric secretion, and sexual functions. L-Histidine is also required for blood cell manufacture and protects tissues against damage caused by radiation and heavy metals.

IMT1 (Propanamide, N,N-dimethyl-2-[[4-(2-methylphenyl)-2-oxo-2H-1-benzopyran-7-yl]oxy]-) has anticancer activity.

VLX600 is an iron-chelating oxidative phosphorylation (OXPHOS) inhibitor, is a cell-permeable anticancer agent. It acts by reducing mitochondrial oxidative phosphorylation in tumor cells.

BI-6C9 is an inhibitor of tBid (Kd = 20 µM).BI-6c9 prevented MOMP and mitochondrial fission, and protected the cells from cell death.

Fumarate hydratase-IN-1 is a cell-permeable fumarate hydratase inhibitor with antiproliferative activity and can be used to study cellular activity.

Gboxin is an inhibitor of oxidative phosphorylation that targets glioblastoma,inhibits the activity of F0F1 ATP synthase, with antitumour activity.

Azemiglitazone (MSDC 0602) is an insulin sensitizer potentially for the treatment of diabetes.

ER-000444793 is a potent mitochondrial permeability transition pore (mPTP) opening inhibitor and it also inhibits mPTP (IC50: 2.8 μM).

Genistein 8-c-glucoside (G8CG) induces mitochondrial membrane depolarization and induces apoptosis. Genistein 8-c-glucoside (G8CG) is a natural glucoside isolated from flowers of Lupinus luteus L.

Glutamate dehydrogenase NAD(P) (GLDH) is a mitochondrial enzyme widely found in organisms that catalyzes the reversible oxidative deamination of glutamate to produce α-ketoglutarate (α-KG), which is used in the study of diseases caused by abnormalities in glutamate metabolism.

CCI-006, a selective inhibitor and chemosensitizer for MLL-rearranged leukemia cells, disrupts mitochondrial respiration. This action leads to irreversible mitochondrial depolarization and triggers a pro-apoptotic unfolded protein response in specific MLL-r leukemia cells.

Mito-LND (Mito-Loidamine) is an orally active and mitochondria-targeted inhibitor of oxidative phosphorylation.