Background:Metabolic pathways are fundamental to cellular function, providing the energy and building blocks necessary for growth, maintenance, and response to environmental changes. Dysregulation of metabolic enzymes and pathways is linked to a variety of diseases, including cancer, metabolic disorders, and neurodegenerative diseases. Targeting these pathways through drug discovery allows for the development of therapies that can correct metabolic imbalances or exploit metabolic vulnerabilities in diseased cells.

Key Metabolic Targets and Assay Technologies:

1. Glucose Metabolism:

    G6PD (Glucose-6-phosphate dehydrogenase): Essential for the pentose phosphate pathway, providing reducing power and nucleotide precursors.

    IDH1 R132H, IDH2 R140Q: Mutations in these isocitrate dehydrogenase enzymes are involved in the metabolic reprogramming observed in certain cancers.

    LDHA/B (Lactate Dehydrogenase A/B): Key enzymes in glycolysis, converting pyruvate to lactate, often upregulated in cancer cells.

    PFKFB3 (6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3): A critical regulator of glycolysis, promoting the synthesis of fructose-2,6-bisphosphate, an allosteric activator of glycolysis.

2. Adenosine Metabolism:

    MTAP (Methylthioadenosine Phosphorylase): Plays a role in polyamine biosynthesis and the salvage of adenine and methionine, often deleted in cancers.

3. Amino Acid Metabolism:

    MAT2A (Methionine Adenosyltransferase 2A): Involved in the synthesis of S-adenosylmethionine (SAM), a key methyl donor in various biochemical reactions.

    IL4I1 (Interleukin 4 Induced 1): Associated with the metabolism of amino acids and modulating immune responses.

4. Nucleotide Metabolism:

    DHODH (Dihydroorotate Dehydrogenase): Catalyzes a key step in the de novo synthesis of pyrimidines, crucial for DNA and RNA synthesis.

    IMPDH1/2 (Inosine Monophosphate Dehydrogenase 1/2): Involved in the synthesis of guanine nucleotides, important for DNA/RNA synthesis and cellular proliferation.

5. Lipid Metabolism:

    CES1/2 (Carboxylesterase 1/2): Enzymes that hydrolyze esters and amides, playing a role in drug metabolism and detoxification.

    MGLL (Monoacylglycerol Lipase): Involved in lipid metabolism, hydrolyzing monoacylglycerols to free fatty acids and glycerol, implicated in cancer and obesity.

    HAO1 (Hydroxyacid Oxidase 1): Plays a role in glyoxylate metabolism and detoxification processes.

Assay Techniques:Our assays utilize advanced technologies such as Fluorescence Intensity (FI), Absorbance-based assays, and Fluorescence Polarization (FP) to provide precise measurements of enzyme activity and inhibition. These methods allow for the detailed characterization of metabolic enzymes, facilitating the discovery and development of inhibitors or modulators that can effectively target these pathways.

Comprehensive Evaluation Services:We offer a wide range of services tailored to the specific needs of our clients, including the screening of small molecules, evaluating enzyme kinetics, and assessing the selectivity of inhibitors across multiple metabolic targets. Our assays are designed to provide high-quality data that supports the development of novel therapeutics aimed at correcting metabolic dysregulation or targeting specific metabolic pathways in diseases.