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
Identifiers
IUPAC name
  • N-(3-Bromo-4-fluorophenyl)-N′-hydroxy-4-{[2-(sulfamoylamino)ethyl]amino}-1,2,5-oxadiazole-3-carboximidamide
CAS Number
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC11H13BrFN7O4S
Molar mass438.23 g·mol−1
3D model (JSmol)
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]

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, Benoit J.; Van Baren, Nicolas; Baurain, Jean-François (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.
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