KL1333

KL1333 is a substrate for NAD(P)H:quinone acceptor oxioreductase 1 (NQO1) and a derivative of the quinone β-lapachone (Item No. 15021).¹ It is converted by NQO1 to NAD⁺ and increases the ratio of NAD⁺ to NADH in a cell-free assay, as well as C2C12 and L6 myoblasts, when used at concentrations of 1, 1, or 2 µM, respectively. KL1333 (1 µM) increases intracellular ATP levels, as well as decreases intracellular lactate and reactive oxygen species (ROS) levels, in primary fibroblasts isolated from patients with the inborn error of metabolism mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). It increases the levels of mitochondrial complex I, also known as NADH dehydrogenase, and mitochondrial complex III, also known as cytochrome bc1 complex, as well as increases the oxygen consumption rate (OCR), in primary fibroblasts isolated from patients with MELAS when used at a concentration of 1 µM. KL1333 (1 µM) inhibits apoptosis, the production of mitochondrial ROS, and mitochondrial membrane depolarization induced by the DNA-crosslinking agent cisplatin (Item No. 13119) in primary mouse cochlear organ of Corti cells.²

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1. Seo, K.-S., Kim, J.-H., Min, K.-N., et al. KL1333, a novel NAD⁺ Modulator, improves energy metabolism and mitochondrial dysfunction in MELAS fibroblasts. Front. Neurol. 9, 552 (2018).

2. Lee, H.-S., Kim, Y.-R., Lee, I.-K., et al. KL1333, a derivative of β-lapachone, protects against cisplatin-induced ototoxicity in mouse cochlear cultures. Biomed. Pharmacother. 126, 110068 (2020).