Isocitrate Dehydrogenase Assay Services

Creative Biolabs offers isocitrate dehydrogenase assay services. Thanks to their outstanding methodology and meticulous approach, Creative Biolabs has solidified a good name in the epigenetic screening assay. We offer rapid, precise testing for a variety of isocitrate dehydrogenase mutations.

Over 80% of low-grade gliomas (LGGs) and subsequent glioblastomas have been shown to contain mutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2). Similar driver mutations in IDH1 and IDH2 have been found in chondrosarcoma, myelodysplastic syndromes, cholangiocarcinoma, and acute myeloid leukemia (AML). IDH1 and IDH2 are homodimeric isoenzymes that play a key role in the oxidative decarboxylation of isocitrate to α-ketoglutarate, which is a crucial mechanism for the synthesis of NADPH in cells. IDH2 is an enzyme located in the mitochondria, whereas IDH1 is present in the cytosol and peroxisomes. Concurrently, substantial reductions in NADPH generation are observed. Initial investigations into the structure and pharmacokinetics of mutant IDH reveal that it gains a stronger affinity for the substrate α-ketoglutarate as well as the cofactor NADPH.

Fig.1. The mutIDH1 and mutIDH2 pathways.¹

Targets of Demethylase Assay Services

All oncogenic IDH mutations reported so far are genetically heterozygous, suggesting that the mutant IDH's critical role is linked to its gain-of-function for converting the wild-type IDH product, α-ketoglutarate, to 2HG, even though the mutant IDH enzyme can coexist in cancer cells as a heterodimer or homodimer with the wild-type IDH. Creative Biolabs' isocitrate dehydrogenase assays are below:

The finding of neomorphic mutations in IDH in a number of cancer types, such as AML and gliomas, has sparked intense investigation and medication development efforts. To enable admission into clinical trials, a variety of currently available mutIDH inhibitors are constantly being modified for pharmacokinetic and pharmacodynamic improvement. Unique mutIDH-associated global DNA hypermethylation patterns (CIMP) in gliomas could not be easily reversible with mutIDH inhibition and 2HG depletion alone. On the other hand, mutIDH inhibition has been shown in multiple investigations using cellular models of AML to easily reverse DNA hypermethylation.

Creative Biolabs offers isocitrate dehydrogenase assay services to discover mutIDH inhibitors. Demethylating medicines, such as DNMT inhibitors or histone-modifying drugs, may enhance response rate and duration across IDH-mutant malignancies, and so should be the focus of our efforts to increase mutIDH inhibitor efficacy. Please contact us for more information about our isocitrate dehydrogenase assay services.

Reference

1. Golub, Danielle, et al. "Mutant isocitrate dehydrogenase inhibitors as targeted cancer therapeutics." Frontiers in oncology 9 (2019): 417.