rate limiting enzyme

Fenclonine (CP-10188) is a selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine(CP-10188) acts pharmacologically to deplete endogenous levels of serotonin.

CIL56 (CA3) is a small molecule that induces cellular ferroptosis through the production of iron-dependent reactive oxygen species (ROS). It also induces accumulation of long-chain saturated, monounsaturated, and polyunsaturated fatty acids in HT-1080 cells in vitro.HT-1080 cells lacking acetyl-CoA carboxylase 1 (ACC1), the rate-limiting enzyme in fatty acid synthesis, exhibit 5-fold resistance to CIL56 treatment, indicating ACC1 activity sensitizes cells to CIL56-induced cell death.

Fenclonine hydrochloride is a selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin.

Meglutol (3-Hydroxy-3-methylglutaric acid) is an antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids. It acts by interfering with the enzymatic steps involved in the conversion of acetate to hydroxymethyl glutaryl coenzyme A as well as inhibiting the activity of HYDROXYMETHYLGLUTARYL COA REDUCTASES which is the rate-limiting enzyme in the biosynthesis of cholesterol.

Glycerol-3-phosphate dehydrogenase from Saccharomyces cerevisiae is an enzyme that catalyzes the oxidation of glycerol-3-phosphate (G3P) to dihydroxyacetone phosphate (DHAP), playing a crucial role in glycerol metabolism and energy production. This enzyme acts as the rate-limiting step in glycerol production within Saccharomyces cerevisiae, regulating glycerol formation and accumulation to aid the yeast in adapting to hyperosmotic environments. Additionally, glycerol-3-phosphate dehydrogenase from Saccharomyces cerevisiae is relevant in research within the field of metabolic engineering.

SAT-IN-3 is a novel inhibitor of salmonella serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis.

Tyrosinase (Polyphenol oxidase) is a key rate-limiting enzyme encoded by the TYR gene that controls melanin production and catalyzes tyrosine oxidation. It is mainly found in melanosomes and plays an important role in melanogenesis, plant secondary metabolism, wound healing and immune response.

MS7 is a potent inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD+ biosynthesis pathway that converts nicotinamide to nicotinamide mononucleotide, which is subsequently transformed into NAD+. NAMPT is overexpressed in various cancer cells to sustain the NAD+ supply required for rapid proliferation. The derivative of MS7, PROTAC A7, serves as an effective NAMPT degrader. MS7 is utilized in cancer research.

KHK-IN-3 (Example 1), a ketohexokinase (KHK) inhibitor, plays a crucial role in the study of various diseases including kidney disease, nonalcoholic steatohepatitis (NASH), diabetes, and heart failure. KHK, a pivotal rate-limiting enzyme and fructokinase, facilitates the metabolism of fructose by catalyzing the transformation of fructose into fructose-1-phosphate (FIP) utilizing ATP. This process lacks feedback inhibition, leading to the buildup of metabolites involved in lipogenesis, gluconeogenesis, and oxidative phosphorylation [1].

hDHODH-IN-12 is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), exhibiting an inhibitory concentration (IC50) of 0.421 μM. As the rate-limiting enzyme in the de novo synthesis of pyrimidines, critical for DNA RNA synthesis, DHODH is localized within the inner membrane of human mitochondria. hDHODH-IN-12 is applicable in lung cancer research [1].

The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in

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].

ALT-007 is an orally bioavailable inhibitor of serine palmitoyltransferase (SPT), the rate-limiting enzyme in de novo ceramide synthesis. In murine models of age-related sarcopenia, ALT-007 effectively restores muscle mass and function impaired by aging. Additionally, ALT-007 may enhance protein homeostasis in Caenorhabditis elegans and in mouse models of aging and age-associated diseases, acting as a ceramide inhibitor.

Pantothenate Kinase Inhibitor (PANKi) is a reversible inhibitor of pantothenate kinase (PanK; IC50s = 70, 92, and 25 nM for PanK1β, PanK2, and PanK3, respectively), the rate-limiting enzyme in the synthesis of coenzyme A .1It binds to the ATP-PanK3 complex with an apparent binding constant of 300 nM and exhibits mixed-type inhibition with respect to ATP and pantothenate. PANKi inhibits CoA biosynthesis in C3A cells (IC50= 0.9 μM) with no effect on cell viability when used at concentrations up to 8 μM. PANKi (5 μM) synergizes with BSO to induce ferroptosis in PANC-1 cells and sensitizes the cells to imidazole ketone erastin-induced ferroptosis.2 1.Sharma, L.K., Leonardi, R., Lin, W., et al.A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinasesJ. Med. Chem.58(3)1563-1568(2015) 2.Badgley, M.A., Kremer, D.M., Maurer, H.C., et al.Cysteine depletion induces pancreatic tumor ferroptosis in miceScience368(6486)85-89(2020)

α-Methyl-DL-aspartic acid serves as a specific inhibitor for the enzyme argininosuccinate synthase (ASS), which is the rate-limiting enzyme in the recycling pathway from 1-citrulline to 1-arginine [1].

SBI-797812 is structurally similar to active-site directed inhibitor of NAMPT(NAMPT with EC50 of 0.37 μM).