| Stereochemistry | ABSOLUTE |
| Molecular Formula | C28H22ClF3N6O3 |
| Molecular Weight | 582.961 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
FC1=CN=CC(=C1)N([C@H](C(=O)NC2CC(F)(F)C2)C3=CC=CC=C3Cl)C(=O)[C@@H]4CCC(=O)N4C5=NC=CC(=C5)C#N
InChI
InChIKey=WIJZXSAJMHAVGX-DHLKQENFSA-N
InChI=1S/C28H22ClF3N6O3/c29-21-4-2-1-3-20(21)25(26(40)36-18-11-28(31,32)12-18)37(19-10-17(30)14-34-15-19)27(41)22-5-6-24(39)38(22)23-9-16(13-33)7-8-35-23/h1-4,7-10,14-15,18,22,25H,5-6,11-12H2,(H,36,40)/t22-,25-/m0/s1
Ivosidenib (AG-120) is an inhibitor of isocitrate dehydrogenase 1 (IDH1) This experimental drug inhibits mutant IDH1, leading to increased differentiation and decreased proliferation in IDH1 positive tumors and thus is thought to be promising for the treatment of IDH1-mutated tumors. In vivo treatment with AG-120 of TF-1 cells, primary human AML patient samples expressing mutant IDH1 and primary human blast cells cultured ex vivo showed that AG-120 is effective at lowering 2-HG levels and restoring cellular differentiation. It showed promising results in a phase I trial in patients with relapsed or refractory acute myeloid leukemia and is being evaluated in Phase III in previously-treated subjects with nonresectable or metastatic cholangiocarcinoma with an IDH1 mutation.
Originator
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
PubMed
Sample Use Guides
Patients in the study were given either 100 mg of AG-120 twice daily, or 300 mg, 500 mg, or 800 mg once daily, over continuous 28-day cycles.
Route of Administration:
Oral
TF-1 cells or primary human AML patient samples expressing mutant IDH1 were treated with 0.5, 1.0, and 5.0 uM of AG-120 which decreased intracellular 2-HG levels, inhibited growth factor independent proliferation and restored erythropoietin (EPO)-induced differentiation in TF-1 IDH1-R132H cells.
ACTIVE MOIETY
