Epacadostat

Epacadostat (previously INCB24360) is an investigational drug for cancer.^[1] Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).^[1][2][3] Epacadostat inhibits IDO1 by competitively blocking it, without interfering with IDO2 or tryptophan 2,3-dioxygenase (TDO). It has antitumor activity in some models, though is most effective when combined with other immunotherapy agents.^[4]

Epacadostat

Clinical data
ATC code	L01XX58 (WHO)
Identifiers
IUPAC name (Z)-N-(3-Bromo-4-fluorophenyl)-N'-hydroxy-4-{[2-(sulfamoylamino)ethyl]amino}-1,2,5-oxadiazole-3-carboximidamide
CAS Number	1204669-58-8
DrugBank	DB11717
ChemSpider	34448418
UNII	71596A9R13
KEGG	D11049
Chemical and physical data
Formula	C11H13BrFN7O4S
Molar mass	438.23 g·mol−1
3D model (JSmol)	Interactive image
SMILES c1cc(c(cc1N/C(=N\O)/c2c(non2)NCCNS(=O)(=O)N)Br)F
InChI InChI=1S/C11H13BrFN7O4S/c12-7-5-6(1-2-8(7)13)17-11(18-21)9-10(20-24-19-9)15-3-4-16-25(14,22)23/h1-2,5,16,21H,3-4H2,(H,15,20)(H,17,18)(H2,14,22,23) Key:FBKMWOJEPMPVTQ-UHFFFAOYSA-N

History and clinical trials

As of 2017, the combination of epacadostat with pembrolizumab (Keytruda) was being investigated by Incyte and Merck & Co. in several cancers, as was the combination of epacadostat with nivolumab (Opdivo) by Incyte and Bristol Myers Squibb.^[5]

In April 2018, Incyte announced they were halting the Phase III ECHO-301/KEYNOTE-252 (NCT02752074) trial of epacadostat with pembrolizumab for melanoma as the combination therapy missed the first primary endpoint of improving progression-free survival vs. pembrolizumab alone.^[6][7] The second primary endpoint of overall survival is not yet determined.^[6]