Glucose 1-dehydrogenase

Glucose 1-dehydrogenase, also known as glucose dehydrogenase (FAD) Pseudomonas glucose dehydrogenase, is an enzyme that catalyzes the conversion of glucose and NAD(P) into NAD(P)H and gluconic acid, serving as a cofactor regeneration mechanism [1].

NCT-502 (N-(4,6-dimethylpyridin-2-yl)-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-carbothioamide) is a human phosphoglycerate dehydrogenase inhibitor, cytotoxic to PHGDH-dependent cancer cells. It decreases glucose-derived serine production and it has an IC50 of 3.7 μM against PHGDH.

Diallyl tetrasulfide is an organosulfur compound that has been found in A. sativum and has diverse biological activities, including antimicrobial, antioxidant, and anticancer properties.[1],[2],[3],[4] It is active against the bacteria S. aureus and methicillin-resistant S. aureus (MRSA; MICs = 0.5 and 2 mg/L, respectively), as well as the fungi C. albicans, C. krusei, C. glabrata, A. niger, A. flavus, and A. fumigatus (MICs = 0.5, 4, 2, 1, 2, and 4 mg/L, respectively).[1] It reduces cadmium-induced increases in hepatic levels of thiobarbituric acid reactive substances (TBARS) and increases cadmium-induced decreases in the hepatic activity of superoxide dismutase (SOD1), catalase, GST, and glucose-6-phosphate dehydrogenase (G6PDH) in rats when administered at a dose of 40 mg/kg.[2] Diallyl tetrasulfide is cytotoxic to MCF-7 breast cancer cells (IC50 = 92 μM) and reduces tumor growth in a BGC-823 mouse xenograft model when administered at doses of 20, 30, and 40 mg/kg for 32 days.[3],[4]

Glucose dehydrogenase (GDH) is an oxidoreductase enzyme that facilitates the oxidation of β-D-glucose into β-D-glucono-1,5-lactone, while concurrently reducing cofactor NADP+ to NADPH, and to a lesser degree, NAD+ to NADH. It can utilize both NAD+ and NADP+ as cofactors and serves in the regeneration of NADH and NADPH [1] [2].

PF-07238025, a potent branched-chain ketoacid dehydrogenase kinase (BDK) inhibitor with an EC50 of 19 nM, enhances the stability of the BDK-BCKDH core E2 subunit interaction and inhibits the phosphorylation of the E1 subunit. By modulating BDK, which regulates the phosphorylation of BCKDH, a key enzyme in branched-chain amino acid (BCAA) degradation, PF-07238025 indirectly controls the rate-limiting step in BCAA catabolism. Dysregulated BCAA metabolism is implicated in various cardiometabolic disorders such as heart failure (HF), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and obesity. Notably, PF-07238025 has been shown to ameliorate cardiometabolic endpoints and enhance glucose tolerance in mouse models [1].