Isocitrate dehydrogenase 1 (NADP+), soluble mRNA (IDH1 mRNA)

Isocitrate dehydrogenase 1 (IDH1) mRNA is the messenger RNA transcript that encodes the cytosolic IDH1 enzyme, which facilitates the conversion of isocitrate to alpha-ketoglutarate (α-KG) while generating NADPH (NCBI Gene: 3417). In various malignancies, including low-grade gliomas and acute myeloid leukemia, somatic mutations in the IDH1 gene (most notably at residue R132) lead to a neomorphic enzyme activity that produces the oncometabolite D-2-hydroxyglutarate (2-HG) (UniProt: O75874). While most therapeutic interventions utilize small-molecule inhibitors to target the mutant protein, the IDH1 mRNA itself is an emerging target for RNA-based therapies such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) (PMID: 23539233). These modalities aim to reduce the expression of the IDH1 protein, thereby lowering 2-HG levels and promoting cellular differentiation in tumor cells. Key challenges in targeting IDH1 mRNA include ensuring specific delivery to tumor tissues, particularly across the blood-brain barrier for gliomas, and avoiding the suppression of wild-type IDH1 in healthy tissues where it is essential for redox balance (PMID: 23139211).

Other names

IDH1 transcriptIDH1 messenger RNAIsocitrate dehydrogenase [NADP] cytoplasmic mRNANADP(+)-specific isocitrate dehydrogenase, cytosolic mRNA

Degradation of IDH1 mRNA via RNA interference or antisense-mediated RNase H cleavage, leading to reduced IDH1 protein synthesis and decreased production of the oncometabolite 2-hydroxyglutarate (PMID: 23139211).