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)

VBIT-4 is a voltage-dependent anion channel 1 (VDAC1) oligomerization inhibitor (Kd: 17 μM). VBIT-4 can be used for therapeutic purposes in apoptosis-associated disorders (such as neurodegenerative and cardiovascular diseases).

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.

Ammonium formate (Formic acid ammonium salt) is the simplest carboxylic acid. Formate is an intermediate in normal metabolism. It is responsible for both metabolic acidosis and disrupting mitochondrial electron transport and energy production by inhibiting cytochrome oxidase activity, the terminal electron acceptor of the electron transport chain. Cell death from cytochrome oxidase inhibition by formate is believed to result partly from depletion of ATP, reducing energy concentrations so that essential cell functions cannot be maintained. Furthermore, inhibition of cytochrome oxidase by formate may also cause cell death by increased production of cytotoxic reactive oxygen species (ROS) secondary to the blockade of the electron transport chain.

Ciprofloxacin monohydrochloride (Bay-09867 hydrochloride) is a broad-spectrum antimicrobial carboxyfluoroquinoline.

Speract TFA is a sea urchin egg peptide that regulates sperm motility, also stimulates sperm mitochondrial metabolism.

Glutathione arsenoxide hydrochloride (Glutathione arsenoxide hydrochloride(1271726-51-2 Free base)) is a potentially active anti-cancer molecule and inhibitor of tumour metabolism. glutathione arsenoxide hydrochloride targets the mitochondrial inner membrane adenine nucleotidyl transferase (ANT), which inhibits cell proliferation and promotes apoptosis. Glutathione arsenoxide hydrochloride can be used to recognize cell surface proteins such as protein disulfide isomerases.

MSDC-0602K (Azemiglitazone potassium) (Azemiglitazone potassium) is a PPARγ-sparing thiazolidinedione (Ps-TZD) compound that binds to PPARγ with an IC50 of 18.25 μM. It also modulates the mitochondrial pyruvate carrier (MPC). This compound, MSDC-0602K, has potential applications in researching fatty liver conditions, including dysfunctional lipid metabolism, inflammation, and insulin resistance. MSDC-0602K acts as an insulin sensitizer, improving insulinemia and fatty liver disease in mice both individually and in combination with Liraglutide.

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).

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

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.

1. Cornuside (Comuside) has immunomodulatory activity . 2. Cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells. 3. Cornuside can treat myocardial I/R and protect the liver from CCl4-induced acute hepatotoxicity, by reducing oxidative stress and suppressing inflammatory responses. 4. Cornuside has anti-inflammatory activity by downregulations of iNOS and COX-2 due to NF-κB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells. 5. Cornuside has protective potential against cerebral ischemic injury, may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.

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

Perhexiline is an orally active inhibitor of CPT1 and CPT2 that reduces fatty acid metabolism. Perhexiline can cross the blood-brain barrier (BBB) and exhibits anti-tumor activity. Perhexiline induces mitochondrial dysfunction and apoptosis in hepatocytes. Therefore, Perhexiline can be used in cancer and cardiovascular disease research [1] [2] [5].

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.

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.

TRAP1-IN-1 (compound 35) is a potent, selective TRAP1 inhibitor affecting the mitochondrial variant of Hsp90. It exhibits over 250-fold greater selectivity for TRAP1 compared to Grp94, destabilizes TRAP1 tetramers, and promotes the degradation of TRAP1 client proteins. Additionally, TRAP1-IN-1 impedes mitochondrial complex I activity involved in oxidative phosphorylation OXPHOS, compromises the mitochondrial membrane potential, and augments glycolytic metabolism [1].

ms2i6A is a mitochondrial tRNA-specific modification, which regulates efficient mitochondrial translation and energy metabolism in mammals.

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

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.

Ninerafaxstat hifts cellular metabolism from fatty acid oxidation to glucose oxidation.Ninerafaxstat decreases fatty acid oxidation and improve overall mitochondrial respiration.Ninerafaxstat inhibit the growth and proliferation of cancer cells [1].

N-Isovaleroylglycine (Isovaleroylglycine) is an acyl glycine. Acyl glycines are normally minor metabolites of fatty acids. However, the excretion of certain acyl glycines is increased in several inborn errors of metabolism. In certain cases, the measurement of these metabolites in body fluids can be used to diagnose disorders associated with mitochondrial fatty acid beta-oxidation. Acyl glycines are produced through the action of glycine N-acyltransferase which is an enzyme that catalyzes the chemical reaction: acyl-CoA + glycine < -- > CoA + N-acylglycine. N-Isovaleroylglycine is a byproduct of the catabolism of the amino acid leucine. Accumulation of N-Isovaleroylglycine occurs in Isovaleric Acidemia (IVA).

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.

NCI-006 is a potent new inhibitor of lactate dehydrogenase (LDH) that disrupts tumor growth in mice. LDH inhibition slows tumor growth but rapidly redirects pyruvate to support mitochondrial metabolism. Inhibiting both mitochondrial complex 1 and LDH suppresses metabolic plasticity of glycolytic tumors in vivo, significantly prolonging tumor growth inhibition.

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.

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.

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.

Quinine sulfate dihydrate plays a major role in potassium channel blockers. It is also used as an antimalarial, anticholinergic, antihypertensive and a hypoglycemic agent. It inhibits mitochondrial ATP-regulated potassium channel. It is also used to study the metabolism of biocrystalized heme, hemozoin, in malarial parasites and to study the toxicity of heme (FP)-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).

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

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.

Ninerafaxstat trihydrochloride shifts cellular metabolism to glucose oxidation from fatty acid oxidation. Ninerafaxstat trihydrochloride improves overall mitochondrial respiration and reduces fatty acid oxidation, thereby inhibiting the proliferation and growth of cancer cells.

THP104c is an inhibitor of mitochondrial fission.

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

Erythronic acid, an endogenous carbohydrate metabolite, is instrumental for research into metabolism-associated disorders. It significantly influences both the development and amelioration of hyperuricemia and is associated with mitochondrial dysfunction in cases of transaldolase deficiency [1].

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.

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.

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.

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

Ciprofloxacin (Bay-09867), a synthetic broad spectrum fluoroquinolone antibiotic, inhibits bacterial DNA gyrase. It is more active against Gram-negative bacteria than Gram-positive bacteria.

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.

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

Antimalarial agent 14 (NSC-102533) is a bioactive chemical.