Mitoquinone-cyclodextrin is a 1:1 molar ratio complex of Mitoquinone mesylate with cyclodextrin. Mitoquinone mesylate is a mitochondria-targeted antioxidant designed to accumulate within mitochondria in vivo in order to protect against oxidative damage. M
VT-ME6 is a potent and selective sphingosine kinase 2 inhibitor. VT-ME6, contained a quaternary ammonium group as a warhead and established that a positively charged moiety is necessary for engaging key amino acid residues in the enzyme binding pocket.13,14 This compound is moderately potent (Ki = 8 lM) and displays three-fold selectivity for SphK2 over SphK1. Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis, and sickle cell disease.
Coenzyme Q10 is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. In its reduced form, it acts as an antioxidant. Coenzyme Q2 is a precursor of coenzyme Q10 that has 2, rather than 10, isoprenoid units on the ubiquinone base. It can act as an electron acceptor for bacterial Complex I. In mammalian cells, exogenous coenzyme Q2 prevents the production of reactive oxygen species associated with Complex I activity. Forms of coenzyme Q with shorter isoprenoid chains, including coenzyme Q2, induce p53-dependent apoptosis in human B-cell acute lymphoblastoid leukemia BALL-1 cells.
CAY10748 is an agonist of stimulator of interferon genes (STING; IC50= 0.3794 μM in a competition binding assay).1It activates STING in STING-expressing, but not STING knockout, THP-1 cells (EC50s = 0.287 and >100 μM, respectively, in a reporter assay). It induces phosphorylation of STING at the serine in position 366, as well as phosphorylation of TBK1 and IFN regulatory factor 3 (IRF3), indicating activation of the STING-TBK1-IRF3 signaling pathway. CAY10748 increases the secretion of IFN-β and the levels of chemokine (C-X-C motif) ligand 10 (CXCL10), and IL-6 in peripheral blood mononuclear cells (PBMCs) when used at a concentration of 10 μM. It also reduces tumor growth in a CT26 murine colon cancer model when administered at a dose of 0.15, but not 1.5, mg/kg. 1.Xi, Q., Wang, M., Jia, W., et al.Design, synthesis, and biological evaluation of amidobenzimidazole derivatives as stimulator of interferon genes (STING) receptor agonistsJ. Med. Chem.63(1)260-282(2019)