Description
AG-120 is an orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1) that specifically inhibits a mutated form of IDH1 in the cytoplasm, preventing the formation of 2-hydroxyglutarate. AG-120 may induce cellular differentiation as well as inhibit proliferation in IDH1-expressing tumor cells.
Uses
Ivosidenib is a first-in-class mutant IDH1 inhibitor for the treatment of IDH1 mutant cancers.
Definition
ChEBI: Ivosidenib is a tertiary carboxamide resulting from the formal condensation of the carboxy group of (2S)-1-(4-cyanopyridin-2-yl)-5-oxopyrrolidine-2-carboxylic acid with the secondary amino group of (2S)-2-(2-chlorophenyl)-N-(3,3-difluorocyclobutyl)-2-[(5-fluoropyridin-3-yl)amino]acetamide. It is approved by the FDA for the treatment of acute myeloid leukemia (AML) in patients with an isocitrate dehydrogenase-1 (IDH1) mutation. It has a role as an antineoplastic agent and an EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor. It is a member of monochlorobenzenes, a cyanopyridine, a member of pyrrolidin-2-ones, an organofluorine compound, a tertiary carboxamide and a secondary carboxamide.
in vitro
tf-1 cells or primary human aml patient samples expressing mutant idh1 were treated with ag-120, and the results showed that in tf-1 idh1-r132h cells, ag-120 was able to decrease the intracellular 2-hg levels, inhibit growth factor independent proliferation and restore erythropoietin-induced differentiation [1].
References
[1] erica hansen et al. ag-120, an oral, selective, first-in-class, potent inhibitor of mutant idh1, reduces intracellular 2hg and induces cellular differentiation in tf-1 r132h cells and primary human idh1 mutant aml patient samples treated ex vivo. blood 2014 124:3734.
[2] http://www. aacr.org/newsroom/pages/news-release-detail.aspx itemid=789#.wlauom997iu
