Epacadostat (INCB024360)
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MedKoo CAT#: 206461

CAS#: 1204669-58-8 (INCB024360)

Description: Epacadostat, also known as INCB024360 or INCB24360, is an orally available hydroxyamidine and inhibitor of indoleamine 2,3-dioxygenase (IDO1), with potential immunomodulating and antineoplastic activities. INCB024360 targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, INCB024360 increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), NK cells, and T-lymphocytes, as well as interferon (IFN) production, and a reduction in tumor-associated regulatory T cells (Tregs).

Chemical Structure

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Epacadostat (INCB024360)
CAS# 1204669-58-8 (INCB024360)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206461
Name: Epacadostat (INCB024360)
CAS#: 1204669-58-8 (INCB024360)
Chemical Formula: C11H13BrFN7O4S
Exact Mass: 436.99
Molecular Weight: 438.230
Elemental Analysis: C, 30.15; H, 2.99; Br, 18.23; F, 4.34; N, 22.37; O, 14.60; S, 7.32

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 950 Ready to ship
1g USD 1650 Ready to ship
2g USD 2950 Ready to ship
5g USD 6550 Ready to ship
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Related CAS #: 1204669-58-8 (INCB024360)   1204669-37-3 (INCB024360)   914471-09-3 (INCB14943)    

Synonym: INCB024360; INCB 024360; INCB-024360; INCB24360; INCB-24360; INCB 24360; Epacadostat; INCB14943-analog; INCB-14943-analog; INCB 14943-analog;

IUPAC/Chemical Name: (Z)-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-((2-(sulfamoylamino)ethyl)amino)-1,2,5-oxadiazole-3-carboximidamide

InChi Key: FBKMWOJEPMPVTQ-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=S(NCCNC1=NON=C1/C(NC2=CC=C(F)C(Br)=C2)=N/O)(N)=O

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO, DMA, etc. Method 1: INCB024360 was reconstituted in 5% DMA, 47.5% propylene glycol. (See J. Med. Chem, 2009, 52(23), 7364. supporting information). Methdod 2: INCB024360 was reconstituted in 3% DMA, 10% (2-Hydroxypropyl) β-Cyclodextrin. (see: Mol. Cancer. Ther. 2010, 9(2), 489. ). Note: DMA = N,N–Dimethylacetamide.

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Related CAS#: INCB024360: CAS#1204669-58-8 (or 1204669-37-3) INCB024360-analog: CAS#914471-09-3

Biological target: Epacadostat (INCB024360) is a potent and selective indoleamine 2,3-dioxygenase (IDO1) inhibitor with IC50 of 10 nM and displays high selectivity over other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO).
In vitro activity: In cellular assays, INCB024360 selectively inhibits human IDO1 with IC(50) values of approximately 10nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO). In coculture systems of human allogeneic lymphocytes with dendritic cells (DCs) or tumor cells, INCB024360 inhibition of IDO1 promotes T and natural killer (NK)-cell growth, increases IFN-gamma production, and reduces conversion to regulatory T (T(reg))-like cells. IDO1 induction triggers DC apoptosis, whereas INCB024360 reverses this and increases the number of CD86(high) DCs, potentially representing a novel mechanism by which IDO1 inhibition activates T cells. Furthermore, IDO1 regulation differs in DCs versus tumor cells. Reference: Blood. 2010 Apr 29;115(17):3520-30. https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)35093-X
In vivo activity: To investigate whether IDO1 inhibition would similarly reverse immune escape in vivo, bearing IDO1-expressing PAN02 pancreatic carcinomas were treated orally with INCB024360. The growth of tumors in syngeneic immunocompetent C57BL/6 mice was inhibited in a dose-dependent fashion, with 37% and 57% TGC, respectively, for 25 and 100 mg/kg INCB024360 (Figure 5A; P < .01). However, tumors growing in immunodeficient Balb/c nu/nu mice were not affected by similar doses of INCB024360 (Figure 5B). The inability of INCB024360 to elicit an antitumor response in the immunodeficient mice was not due to lesser impact on kyn generation, as the compound levels were similar between the 2 strains and kyn-to-trp ratios were, in fact, more affected in the immunodeficient mice (Figure 5C). Therefore, consistent with the proposed mechanism of action, INCB024360 suppresses kyn generation in vivo, and its antitumor activity is mediated by lymphocytes. Reference: Blood. 2010 Apr 29;115(17):3520-30. https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)35093-X

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 87.0 198.53
Ethanol 87.0 198.53

Preparing Stock Solutions

The following data is based on the product molecular weight 438.23 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol: 1. Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M, Waeltz P, Bowman KJ, Polam P, Sparks RB, Yue EW, Li Y, Wynn R, Fridman JS, Burn TC, Combs AP, Newton RC, Scherle PA. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30. doi: 10.1182/blood-2009-09-246124. Epub 2010 Mar 2. PMID: 20197554.
In vivo protocol: 1. Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M, Waeltz P, Bowman KJ, Polam P, Sparks RB, Yue EW, Li Y, Wynn R, Fridman JS, Burn TC, Combs AP, Newton RC, Scherle PA. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30. doi: 10.1182/blood-2009-09-246124. Epub 2010 Mar 2. PMID: 20197554. 2. Koblish HK, Hansbury MJ, Bowman KJ, Yang G, Neilan CL, Haley PJ, Burn TC, Waeltz P, Sparks RB, Yue EW, Combs AP, Scherle PA, Vaddi K, Fridman JS. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98. doi: 10.1158/1535-7163.MCT-09-0628. Epub 2010 Feb 2. PMID: 20124451.

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1: Song X, Sun P, Wang J, Guo W, Wang Y, Meng LH, Liu H. Design, synthesis, and biological evaluation of 1,2,5-oxadiazole-3-carboximidamide derivatives as novel indoleamine-2,3-dioxygenase 1 inhibitors. Eur J Med Chem. 2020 Jan 11;189:112059. doi: 10.1016/j.ejmech.2020.112059. [Epub ahead of print] PubMed PMID: 31981851.

2: Peng YH, Liao FY, Tseng CT, Kuppusamy R, Li AS, Chen CH, Fan YS, Wang SY, Wu MH, Hsueh CC, Chang JY, Lee LC, Shih C, Shia KS, Yeh TK, Hung MS, Kuo CC, Song JS, Wu S, Ueng SH. Unique sulfur-aromatic interactions contribute to the binding of potent imidazothiazole indoleamine 2,3-dioxygenase inhibitors. J Med Chem. 2020 Jan 21. doi: 10.1021/acs.jmedchem.9b01549. [Epub ahead of print] PubMed PMID: 31961685.

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4: Chu CE, Porten SP, Grossfeld GD, Meng MV. Role of Indoleamine-2,3-Dioxygenase Inhibitors in Salvage Therapy for Non-Muscle Invasive Bladder Cancer. Urol Clin North Am. 2020 Feb;47(1):111-118. doi: 10.1016/j.ucl.2019.09.013. Review. PubMed PMID: 31757294.

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6: Du Q, Feng X, Wang Y, Xu X, Zhang Y, Qu X, Li Z, Bian J. Discovery of phosphonamidate IDO1 inhibitors for the treatment of non-small cell lung cancer. Eur J Med Chem. 2019 Nov 15;182:111629. doi: 10.1016/j.ejmech.2019.111629. Epub 2019 Aug 18. PubMed PMID: 31445231.

7: Venkateswaran N, Lafita-Navarro MC, Hao YH, Kilgore JA, Perez-Castro L, Braverman J, Borenstein-Auerbach N, Kim M, Lesner NP, Mishra P, Brabletz T, Shay JW, DeBerardinis RJ, Williams NS, Yilmaz OH, Conacci-Sorrell M. MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer. Genes Dev. 2019 Sep 1;33(17-18):1236-1251. doi: 10.1101/gad.327056.119. Epub 2019 Aug 15. PubMed PMID: 31416966; PubMed Central PMCID: PMC6719621.

8: Mathsyaraja H, Freie B, Cheng PF, Babaeva E, Catchpole JT, Janssens D, Henikoff S, Eisenman RN. Max deletion destabilizes MYC protein and abrogates Eµ-Myc lymphomagenesis. Genes Dev. 2019 Sep 1;33(17-18):1252-1264. doi: 10.1101/gad.325878.119. Epub 2019 Aug 8. PubMed PMID: 31395740; PubMed Central PMCID: PMC6719623.

9: Feng X, Shen P, Wang Y, Li Z, Bian J. Synthesis and in vivo antitumor evaluation of an orally active potent phosphonamidate derivative targeting IDO1/IDO2/TDO. Biochem Pharmacol. 2019 Oct;168:214-223. doi: 10.1016/j.bcp.2019.07.011. Epub 2019 Jul 12. PubMed PMID: 31306643.

10: Chen S, Guo W, Liu X, Sun P, Wang Y, Ding C, Meng L, Zhang A. Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors. Eur J Med Chem. 2019 Oct 1;179:38-55. doi: 10.1016/j.ejmech.2019.06.037. Epub 2019 Jun 17. PubMed PMID: 31233921.

11: Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, Arance A, Carlino MS, Grob JJ, Kim TM, Demidov L, Robert C, Larkin J, Anderson JR, Maleski J, Jones M, Diede SJ, Mitchell TC. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019 Aug;20(8):1083-1097. doi: 10.1016/S1470-2045(19)30274-8. Epub 2019 Jun 17. PubMed PMID: 31221619.

12: Affolter T, Llewellyn HP, Bartlett DW, Zong Q, Xia S, Torti V, Ji C. Inhibition of immune checkpoints PD-1, CTLA-4, and IDO1 coordinately induces immune-mediated liver injury in mice. PLoS One. 2019 May 21;14(5):e0217276. doi: 10.1371/journal.pone.0217276. eCollection 2019. PubMed PMID: 31112568; PubMed Central PMCID: PMC6528985.

13: Angeli A, Ferraroni M, Nocentini A, Selleri S, Gratteri P, Supuran CT, Carta F. Polypharmacology of epacadostat: a potent and selective inhibitor of the tumor associated carbonic anhydrases IX and XII. Chem Commun (Camb). 2019 May 14;55(40):5720-5723. doi: 10.1039/c8cc09568j. PubMed PMID: 31038135.

14: Zhang Y, Bowman K, Maleski J, Diamond S, Yeleswaram S. Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin-an Intracerebral Microdialysis Study in Sprague-Dawley Rats. Drug Metab Dispos. 2019 Jul;47(7):710-714. doi: 10.1124/dmd.118.084053. Epub 2019 Apr 22. PubMed PMID: 31010933.

15: Poncelet L, Ait-Belkacem R, Marillier R, Gomes B, Stauber J. Target exposure and pharmacodynamics study of the indoleamine 2,3-dioxygenase-1 (IDO-1) inhibitor epacadostat in the CT26 mouse tumor model. J Pharm Biomed Anal. 2019 Jun 5;170:220-227. doi: 10.1016/j.jpba.2019.02.038. Epub 2019 Mar 22. PubMed PMID: 30933897.

16: Kwiatkowska D, Kluska P, Reich A. Beyond PD-1 Immunotherapy in Malignant Melanoma. Dermatol Ther (Heidelb). 2019 Jun;9(2):243-257. doi: 10.1007/s13555-019-0292-3. Epub 2019 Mar 29. Review. PubMed PMID: 30927248; PubMed Central PMCID: PMC6522569.

17: Li A, Barsoumian HB, Schoenhals JE, Caetano MS, Wang X, Menon H, Valdecanas DR, Niknam S, Younes AI, Cortez MA, Welsh JW. IDO1 Inhibition Overcomes Radiation-Induced "Rebound Immune Suppression" by Reducing Numbers of IDO1-Expressing Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. Int J Radiat Oncol Biol Phys. 2019 Jul 15;104(4):903-912. doi: 10.1016/j.ijrobp.2019.03.022. Epub 2019 Mar 21. PubMed PMID: 30905636.

18: Gibney GT, Hamid O, Lutzky J, Olszanski AJ, Mitchell TC, Gajewski TF, Chmielowski B, Hanks BA, Zhao Y, Newton RC, Maleski J, Leopold L, Weber JS. Phase 1/2 study of epacadostat in combination with ipilimumab in patients with unresectable or metastatic melanoma. J Immunother Cancer. 2019 Mar 20;7(1):80. doi: 10.1186/s40425-019-0562-8. PubMed PMID: 30894212; PubMed Central PMCID: PMC6425606.

19: Fu X, Yang Y, Xie J, Pan X, Yang X, Du Z, Hao E. Subcutaneous inoculation position affects the immune environment in CT26 carcinomas. Biochem Biophys Res Commun. 2019 Apr 30;512(2):244-249. doi: 10.1016/j.bbrc.2019.03.042. Epub 2019 Mar 14. PubMed PMID: 30879760.

20: Chen S, Song Z, Zhang A. Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions. Curr Top Med Chem. 2019;19(3):180-185. doi: 10.2174/1568026619666190308131805. Review. PubMed PMID: 30854972.