What is an IDH1 mutation?

What is an IDH1 mutation?

The IDH1 gene mutations involved in CN-AML are somatic mutations, found only in cells that become cancerous. They change a single protein building block (amino acid) in the isocitrate dehydrogenase 1 enzyme, replacing the amino acid arginine at position 132 with another amino acid.

What is an IDH2 mutation?

The IDH2 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. These mutations change single protein building blocks (amino acids) in the isocitrate dehydrogenase 2 enzyme.

How does Ivosidenib work?

This medication is a type of targeted therapy called an isocitrate dehydrogenase-1 (IDH1) inhibitor. Ivosidenib works by targeting and blocking IDH 1 enzyme. In some cancers, this receptor is overactive, causing cells to grow and divide too fast. By inhibiting these, this medication can slow or stop tumor growth.

How are IDH1 and IDH2 mutations related to cancer?

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to α-ketoglutarate (αKG).IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrom …

Where are the missense mutations in IDH1 located?

The IDH1 missense mutations at R132 and IDH2 missense mutations at R172 or R140 reside at the enzymes’ catalytic domains and alter the activity of the enzymes so that α-KG is reduced to D-2-hydroxygluterate (2-HG) that is a competitive inhibitor of α-KG ( Figure 2.5) [71].

Are there any small molecule inhibitors for IDH1?

Several small molecule oral IDH inhibitors have either been developed or are in clinical development. These include the IDH1 inhibitors ivosidenib, olutasidenib, IDH305, and BAY1436032; the IDH2 inhibitor enasidenib; and the dual IDH1/2 inhibitors vorasidenib (AG-881), HMPL-306, and LY3410738 (Table ​(Table1).1).

What is the role of IDH1 in lipid metabolism?

IDH1 plays a crucial role in lipid metabolism, promoting glycogenesis during hypoxia by catalyzing the reductive carboxylation of α-ketoglutarate dehydrogenase to acetyl-CoA for lipid biosynthesis. Fazila Asmar, Kirsten Grønbæk, in Epigenetic Cancer Therapy, 2015