Misplaced Pages

Epacadostat

Clinical data
ATC code	L01XX58 (WHO)
Identifiers
IUPAC name (Z)-N-(3-Bromo-4-fluorophenyl)-N'-hydroxy-4-{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
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

Epacadostat (previously INCB24360) is an investigational drug for cancer. Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1). 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.

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.

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. The second primary endpoint of overall survival is not yet determined.

References

1. ^ "Epacadostat". NCI Drug Dictionary. National Cancer Institute. 2011-02-02.
2. Brochez L, Chevolet I, Kruse V (May 2017). "The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy". European Journal of Cancer. 76: 167–182. doi:10.1016/j.ejca.2017.01.011. PMID 28324751.
3. Yue EW, Sparks R, Polam P, Modi D, Douty B, Wayland B, et al. (May 2017). "INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology". ACS Medicinal Chemistry Letters. 8 (5): 486–491. doi:10.1021/acsmedchemlett.6b00391. PMC 5430407. PMID 28523098.
4. Van den Eynde BJ, van Baren N, Baurain JF (2020). "Is There a Clinical Future for IDO1 Inhibitors After the Failure of Epacadostat in Melanoma?". Annual Review of Cancer Biology. 4: 241–256. doi:10.1146/annurev-cancerbio-030419-033635.
5. Staton T (3 April 2017). "Racing in lung cancer again (or still), Merck and BMS expand Incyte combo trials". FiercePharma.
6. ^ "Incyte, Merck & Co. Halt Phase III Trial After Epacadostat/Keytruda Combination Fails in Melanoma". 6 April 2018.
7. Walters J (6 April 2018). "Incyte Tumbles After Epacadostat Miss". BioCentury.

• Experimental cancer drugs
• Sulfamides
• Oxadiazoles
• Bromobenzene derivatives
• Fluorobenzene derivatives