mitochondrial function

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.

1-Nonanol (Nonan-1-ol) is a fragrance with antifungal activity that acts by disrupting cell membrane integrity and mitochondrial function.

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

Ammonium chloride acts as a small molecule autophagy inhibitor.Ammonium chloride is a pH-regulating, heteropolar compound that can cause intracellular alkalosis and metabolic acidosis, thereby affecting enzyme activity and influencing processes in biological systems.Ammonium chloride has potential antimicrobial activity. Ammonium Chloride has potential antimicrobial activity and prevents training-induced improvement in mitochondrial respiratory function in male rat flounder muscle.

INT-767 is a potent farnesoid X receptor (FXR)/TGR5 dual agonist that prevents NASH and promotes visceral adipose brown lipogenesis and mitochondrial function for the study of non-alcoholic steatohepatitis.

Naphthazarin (5,8-Dihydroxy-1,4-naphthoquinone) is effective by various cellular mechanisms including oxidative stress, activation of mitochondrial apoptosis-inducing factor (AIF), depolymerization of microtubules, interference with lysosomal function and p53-dependent p21 activation. It triggers apoptosis and has anti-tumor effects

Bavachalcone, a major bioactive compound isolated from *Psoralea corylifolia* L., may serve as a therapeutic drug for bone resorption-associated diseases. It protects endothelial function by increasing AMPK activity and MnSOD expression while reducing mitochondrial oxidative stress.

Dabuzalgron (Ro 115-1240), an orally active selective alpha-1A adrenergic receptor agonist, is used to treat urinary incontinence and prevents doxorubicin-induced cardiotoxicity by maintaining mitochondrial function.

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.

MTP 131 is a mitochondria-targeted peptide antioxidant.1,2It localizes to the mitochondria and reducestert-butyl hydroperoxide-induced lipid peroxidation and apoptosis in SH-SY5Y cells when used at concentrations ranging from 0.001 to 1 nM.1MTP 131 (2 mg kg) reduces infarct volume, hemispheric swelling, and glutathione (GSH) depletion in a mouse model of acute cerebral ischemia induced by middle cerebral artery occlusion (MCAO).2It increases survival, improves motor function, and decreases degeneration of the lumbar spinal cord in a superoxide dismutase 1 mutant (SOD1G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 5 mg kg. MTP 131 reduces albuminuria, urinary hydrogen peroxide levels, and mesangial matrix accumulation, as well as preserves superoxide production, in adb dbmouse model of diabetic nephropathy.3 1.Zhao, K., Luo, G., Giannelli, S., et al.Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell linesBiochem. Pharmacol.70(12)1796-1806(2005) 2.Szeto, H.H.Mitochondria-targeted peptide antioxidants: Novel neuroprotective agentsAAPS J.8(3)E521-E531(2006) 3.Miyamoto, S., Zhang, G., Hall, D., et al.Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db db mice against progression of diabetic kidney diseaseJ. Biol. Chem.295(21)7249-7260(2020)

Bocidelpar is a modulator of PPARδ with an EC50 of 7.80 nM and improves mitochondrial biogenesis and function in Duchenne Muscular Dystrophy muscle cells.

Azoramide, a small-molecule modulator, has the antidiabetic activity of unfolded protein response.

DRX-065 is a stabilized and deuterated R-enantiomer of pioglitazone. DRX-065 has pharmacological properties desirable for the treatment of NASH (mitochondrial function modulation, non-steroidal anti-inflammatory effects, and glucose lowering effects) with

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].

ICA-105665 (PF-04895162) is a potent and orally active opener of neuronal Kv7.2 7.3 and Kv7.3 7.5 potassium channels. ICA-105665 had low cytotoxic potential in human hepatocytes but inhibited liver mitochondrial function and bile salt export protein (BSEP) transport (IC50 of 311 μM). ICA-105665 can penetrate the central nervous system (CNS) and has antiseizure effects [1][2][3][4].

SLU-PP-332 is a pan-estrogen receptor-related receptor (ERR) agonist with high affinity for ERRα, ERRβ, and ERRγ, exhibiting EC50 values of 98, 230, and 430 nM, respectively. SLU-PP-332 enhances mitochondrial function and cellular respiration, increases type IIa oxidized skeletal muscle fibers, and enhances exercise tolerance in skeletal muscle cell lines. It has potential applications in the study of metabolic diseases, improvement of muscle function, and amelioration of metabolic disorders and aging.

FPR2 agonist 2 is a potent FPR2 agonist with blood-brain barrier permeability that acts on h-FPR2 (EC50: 0.13 nM), inhibiting the production of pro-inflammatory cytokines, counteracting changes in mitochondrial function, and inhibiting caspase-3 activity.

OPC-163493 is an orally active, liver-targeted mitochondrial uncoupling agent that diminishes Δψ (delta psi) and mitochondrial ROS (reactive oxygen species) production. This compound demonstrates antidiabetic properties and cardiovascular benefits, including lowering blood pressure, prolonging survival, and enhancing renal function in a rat model of stroke/hypertension [1].

Magmas-IN-1 (compound 9), a small molecule Magmas inhibitor (SMMI), targets the mitochondria-associated granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling molecule and GM-CSF inducible gene in myeloid cells. This compound effectively inhibits Magmas, modulating mitochondrial function, and impedes yeast proliferation at a concentration of 4 μM [1].

Chol-CTPP, a ligand with a dual targeting effect on the blood-brain barrier (BBB) and glioma cells, serves as the precursor to Lip-CTPP when combined with another mitochondria-targeting ligand (Chol-TPP). Lip-CTPP emerges as a potential carrier facilitating the collaborative anti-glioma efficacy of doxorubicin (DOX) and lonidamine (LND). It significantly enhances the inhibition of tumor cell proliferation, migration, and invasion, promotes apoptosis and necrosis, and disrupts mitochondrial function [1].

NS004 is a large-conductance K+ channel opener, it inhibits mitochondrial function in glioma cells.

Z640 an aPKC agonist. Z640 was further confirmed as a non‑selective aPKC agonist that can activate the kinase activity of both PKCι and PKCζ. In the cell‑based assay, Z640 was found to protect neuronal cell lines from amyloid‑β (Aβ) oligomer‑induced cell death by reducing reactive oxygen species production and restore mitochondrial function. In addition, Z640 could reduce Aβ40 generation in a dose‑dependent manner and shift amyloid precursor protein processing towards the non‑amyloid pathway

SCAL-266, a potent inhibitor of mitochondrial complex I (CI), exhibits an IC50 of 0.83 μM. This compound impairs mitochondrial function by blocking oxidative phosphorylation (OXPHOS), inhibiting oxygen consumption rate (OCR), increasing reactive oxygen species (ROS) production, and diminishing mitochondrial membrane potential (MMP). Furthermore, SCAL-266 demonstrates significant antiproliferative activity against OXPHOS-dependent cancer cells [1].

L-Cytidine, an L-configurational form of Cytidine, is a pyrimidine nucleoside and a component of RNA. It influences the glial glutamate cycle, brain phospholipid metabolism, catecholamine synthesis, and mitochondrial function [1] [2].

AP39 is a compound used to increase the levels of hydrogen sulfide (H2S) within mitochondria. It consists of a mitochondria-targeting motif (triphenylphosphonium) coupled to an H2S-donating moiety (dithiolethione) by an aliphatic linker. AP39 (30-300 nM) dose-dependently increases H2S levels in endothelial cells, predominantly in mitochondrial regions. It stimulates mitochondrial electron transport and improves cellular bioenergetic function at lower concentrations (30-100 nM), while having an inhibitory effect at 300 nM. Under oxidative stress conditions induced by glucose oxidase, AP39 has antioxidant and cytoprotective effects. AP39 is effective in vivo, inhibiting voltage-dependent T-type calcium channels and improving hemodynamic parameters in rats.

Decylubiquinone is an analog of ubiquinone. It increases mitochondrial function in synaptosomes. Decylubiquinone inhibits the redox-activated mitochondrial permeability transition.

Compound 6, fac-[Re(CO)3(L6)(H2O)][NO3], a rhenium(I) tricarbonyl aqua complex, serves as an anticancer agent by disrupting mitochondrial function. It exhibits cytotoxicity against prostate cancer cells with an IC50 of 50 nM in PC-3 cells. This compound predominantly localizes in the nucleus, impairs ATP production, and induces apoptosis in PC3 cells without causing necrosis, pyroptosis, or autophagy [1].

CD38 Inhibitor 3 (compound 1), with an IC50 of 11 nM, is a potent agent that enhances mitochondrial biogenesis, diminishes lactate levels, and augments both NAD+ content and Nrf2 expression. In a Pus1 -/- mouse model of mitochondrial myopathy, it also elevates muscle function and bolstering exercise capacity [1].

Vitexin-4''-O-glucoside (Vitexin -4''-O-glucoside) could effectively protect ECV-304 cells against cytotoxicity induced by TBHP through resuming mitochondrial function.

TSPO Ligand-Linker Conjugates 1, comprising a translocator protein (TSPO) ligand and a linker, is instrumental in synthesizing mitochondria-targeting autophagy-targeting chimera (AUTAC). This compound binds TSPO on the outer mitochondrial membrane (OMM), facilitating the degradation of malfunctioning mitochondria and proteins through mitophagy, thereby enhancing mitochondrial function. It holds potential applications in research related to mitochondrial dysfunction, encompassing neurodegenerative diseases, cancer, and diabetes [1].

Elamipretide (MTP-131) is a mitochondria-targeted antioxidant tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) that reduces toxic reactive oxygen species (ROS) production and stabilizes cardiolipin, with blood-brain-barrier permeability. It is a potential therapeutic agent in the rare disease of Barnes syndrome.

Elamipretide 2TFA (RX-31 2TFA) is a novel mitochondrion-targeted antioxidant.

Elamipretide acetate (MTP 131 acetate) is a derivative of Elamipretide, a small mitochondria-targeting tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) that can be used in studies to reduce the production of toxic reactive oxygen species and stabilize cardiolipin.

Elamipretide TFA (RX-31 TFA) is a cardiolipin peroxidase inhibitor and mitochondria-targeting peptide[1].