Mitochondrial Metabolism

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.

Imeglimin hydrochloride (EMD 387008 hydrochloride) is an oral hypoglycemic agent. Imeglimin improves insulin sensitivity, inhibits the production of reactive oxygen species, increases mitochondrial DNA, and improves mitochondrial function.

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

Devimistat (6,8-Bis(benzylthio)octanoic acid) , a lipoate analog, inhibits mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase, disrupts tumor cell mitochondrial metabolism. It has potential chemopreventive and antineoplastic activities, and has been used in trials studying the treatment of Cancer, Lymphoma, Solid Tumors, Advanced Cancer, and Pancreatic Cancer, among others.

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.

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) neurons, but internalization of serotonin transporter (SERT) in serotonergic (5-HT) neurons. MPP+ induces autophagic cell death in SH-SY5Y cells.

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

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

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

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.

Perhexiline maleate is an orally active inhibitor of CPT1 and CPT2, reducing fatty acid metabolism, with IC50 values of 77 μM and 148 μM against rat heart and liver CPT1, respectively.

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

BRD6897 is a mitochondrial content inducer that increases the cellular content of mitochondria and induces a significant increase in the electron density of existing mitochondria.

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

UK-5099 (PF-1005023) is a specific and potent inhibitor of MPC carrier activity, effectively inhibiting pyruvate-dependent oxygen consumption in rat heart mitochondria with an IC50 of 50 nM [1].

MFI8 is a compound that regulates mitochondrial fission and can be used to study aging.

HQNO is a natural product isolated from P. aeruginosa,and is a potent inhibitor of electron transport chain(Kd of 64 nM for complex III). It also is a potent mitochondrial NDH-2 inhibitorin many species.

McN3716 is a carnitine palmitoyltransferase I (CPT-1) inhibitor used for researching metabolic diseases.

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

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

7ACC2 is a new potent MCT inhibitor with IC50 of 11 nM for [14C]-lactate influx; new antitumor treatment targeting lactate transport in Y cells.

BAM 15 is an uncoupler of mitochondrial protonophore.

Adjudin (AF-2364) is a small molecule compound known to possess antispermatogenic function, attenuates microglia activation by suppression of the NF-κB pathway.

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

Afzelin (Kaempferol-3-O-rhamnoside) exhibits several cellular activities such as DNA-protective, antibacterial, antioxidant, anti-inflammatory, and UV-absorbing properties, potentially protecting human skin from UVB-induced damage through a combination of UV-absorbing and cellular actions. Afzelin mitigates mitochondrial damage, promotes mitochondrial biogenesis, and reduces levels of mitophagy-related proteins, parkin and PTEN-induced putative kinase 1.

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

Mitochonic acid 5 (MA-5) is a derivative of the plant hormone indole-3-acetic acid. Mitochonic acid 5 binds mitochondria and ameliorates renal tubular and cardiac myocyte damage.It has been shown to improve survival of fibroblasts from patients with mitochondrial diseases.

Agaricic acid is an adenine nucleotide translocase antagonist.It is obtained from various plants of the fungous tribe, i.e. Polyporus officinalis and Polyporus igniarius. Agaric acid (Agaricinic Acid) induces mitochondrial permeability transition through its interaction with the adenine nucleotide translocase. Agaric acid promotes efflux of accumulated Ca 2+, collapse of transmembrane potential, and mitochondrial swelling. Agaric acid is used to regulate lipid metabolism.

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

MCU-i4 is a novel negative modulator of the MCU, binding MICU1 and impairing muscle cell growth.

KL1333 (NQO1 activator 1) enhances energy metabolism and mitochondrial dysfunction in MELAS fibroblasts. Elevated NAD+ levels trigger the activation of SIRT1 and AMPK, and subsequently activates PGC-1α. NQO1 activator 1 is an orally available NAD+ modulator. It reacts with NAD(P)H: NQO1 as a substrate, resulting in increases in intracellular NAD+ levels via NADH oxidation.

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

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.

NL-1, a mitoNEET inhibitor, exhibits antileukemic effects.

Dihydrorotenone is a potent mitochondrial inhibitor and probably induces Parkinsonian syndrome.

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

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

MitoTracker Orange CMTMRos is a live cell fluorescent dye that labels mitochondria in living cells by mitochondrial membrane potential accumulation and is suitable for live cell imaging and apoptosis studies.

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

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

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

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.

Idebenone (CV-2619) is a synthetic analogue of ubiquinone (Coenzyme Q10), a vital cell antioxidant and essential component of the Electron Transport Chain (ETC).

α-Lipoic Acid (Alphalipoic acid) inhibits NF-κB-dependent HIV-1 LTR activation. α-Lipoic Acid induces endoplasmic reticulum (ER) stress-mediated apoptosis in hepatoma cells.α-Lipoic Acid is an antioxidant, which is an essential cofactor of mitochondrial enzyme complexes.

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).

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.

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.

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.