Tibsovo
Tibsovo (ivosidenib) was approved for the following therapeutic use:
Tibsovo is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) R132 mutation after at least one prior line of systemic therapy.
Ivosidenib is a small molecule inhibitor of R132-mutated isocitrate dehydrogenase 1 (IDH1) enzymes. Through a gain of neomorphic function, the mutant IDH1 converts alpha-ketoglutarate (α-KG) to 2- hydroxyglutarate (2-HG). As 2-HG competitively inhibits α-KG-dependent enzymes, including histone and deoxyribonucleic acid (DNA) demethylases, its accumulation leads to widespread epigenetic dysregulation. Ivosidenib inhibited selected IDH1 mutants (R132C, R132L, R132G, R132H and R132S) at much lower concentrations than wild-type IDH1 in vitro.