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).


Price and Availability

Size
Price

50mg
USD 150
1g
USD 1250
Size
Price

200mg
USD 450
5g
USD 3450
Size
Price

500mg
USD 850
10g
USD 5250

Epacadostat (INCB024360), purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 5g may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206461
Name: Epacadostat (INCB024360)
CAS#: 1204669-58-8 (INCB024360)
Chemical Formula: C11H13BrFN7O4S
Exact Mass: 436.99171
Molecular Weight: 438.23
Elemental Analysis: C, 30.15; H, 2.99; Br, 18.23; F, 4.34; N, 22.37; O, 14.60; S, 7.32


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

Synonym: INCB024360; INCB 024360; INCB-024360; INCB24360; INCB-24360; INCB 24360; Epacadostat

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


Technical Data

Appearance:
White to off-white solid powder

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

Safety Data Sheet (MSDS):

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).

Harmonized System Code:
293490


Additional Information

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


References

1: Yue EW, Sparks R, Polam P, Modi D, Douty B, Wayland B, Glass B, Takvorian A, Glenn J, Zhu W, Bower M, Liu X, Leffet L, Wang Q, Bowman KJ, Hansbury MJ, Wei M, Li Y, Wynn R, Burn TC, Koblish HK, Fridman JS, Emm T, Scherle PA, Metcalf B, Combs AP. INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology. ACS Med Chem Lett. 2017 Mar 6;8(5):486-491. doi: 10.1021/acsmedchemlett.6b00391. eCollection 2017 May 11. PubMed PMID: 28523098; PubMed Central PMCID: PMC5430407.

2: Wu Y, Xu T, Liu J, Ding K, Xu J. Structural insights into the binding mechanism of IDO1 with hydroxylamidine based inhibitor INCB14943. Biochem Biophys Res Commun. 2017 May 27;487(2):339-343. doi: 10.1016/j.bbrc.2017.04.061. Epub 2017 Apr 13. PubMed PMID: 28412361.

3: Maliniemi P, Laukkanen K, Väkevä L, Dettmer K, Lipsanen T, Jeskanen L, Bessede A, Oefner PJ, Kadin ME, Ranki A. Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas. Oncoimmunology. 2017 Feb 10;6(3):e1273310. doi: 10.1080/2162402X.2016.1273310. eCollection 2017. PubMed PMID: 28405495; PubMed Central PMCID: PMC5384345.

4: Brochez L, Chevolet I, Kruse V. The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy. Eur J Cancer. 2017 May;76:167-182. doi: 10.1016/j.ejca.2017.01.011. Epub 2017 Mar 18. Review. PubMed PMID: 28324751.

5: Zhang Q, Zhang Y, Boer J, Shi JG, Hu P, Diamond S, Yeleswaram S. In Vitro Interactions of Epacadostat and its Major Metabolites with Human Efflux and Uptake Transporters: Implications for Pharmacokinetics and Drug Interactions. Drug Metab Dispos. 2017 Jun;45(6):612-623. doi: 10.1124/dmd.116.074609. Epub 2017 Mar 10. PubMed PMID: 28283500.

6: Beatty GL, O'Dwyer PJ, Clark J, Shi JG, Bowman KJ, Scherle PA, Newton RC, Schaub R, Maleski J, Leopold L, Gajewski TF. First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies. Clin Cancer Res. 2017 Jan 4. doi: 10.1158/1078-0432.CCR-16-2272. [Epub ahead of print] PubMed PMID: 28053021.

7: Shi JG, Bowman KJ, Chen X, Maleski J, Leopold L, Yeleswaram S. Population Pharmacokinetic and Pharmacodynamic Modeling of Epacadostat in Patients With Advanced Solid Malignancies. J Clin Pharmacol. 2017 Jun;57(6):720-729. doi: 10.1002/jcph.855. Epub 2016 Dec 19. PubMed PMID: 27990653.

8: Jochems C, Fantini M, Fernando RI, Kwilas AR, Donahue RN, Lepone LM, Grenga I, Kim YS, Brechbiel MW, Gulley JL, Madan RA, Heery CR, Hodge JW, Newton R, Schlom J, Tsang KY. The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells. Oncotarget. 2016 Jun 21;7(25):37762-37772. doi: 10.18632/oncotarget.9326. PubMed PMID: 27192116; PubMed Central PMCID: PMC5122347.

9: Boer J, Young-Sciame R, Lee F, Bowman KJ, Yang X, Shi JG, Nedza FM, Frietze W, Galya L, Combs AP, Yeleswaram S, Diamond S. Roles of UGT, P450, and Gut Microbiota in the Metabolism of Epacadostat in Humans. Drug Metab Dispos. 2016 Oct;44(10):1668-74. doi: 10.1124/dmd.116.070680. Epub 2016 Jul 25. PubMed PMID: 27457784.

10: Dhiman V, Giri KK, S SP, Zainuddin M, Rajagopal S, Mullangi R. Determination of epacadostat, a novel IDO1 inhibitor in mouse plasma by LC-MS/MS and its application to a pharmacokinetic study in mice. Biomed Chromatogr. 2017 Feb;31(2). doi: 10.1002/bmc.3794. Epub 2016 Aug 11. PubMed PMID: 27451018.

11: Shi JG, Chen X, Punwani NG, Williams WV, Yeleswaram S. Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor. J Clin Pharmacol. 2016 Nov;56(11):1344-1354. doi: 10.1002/jcph.737. PubMed PMID: 26990117.

12: Zhai L, Spranger S, Binder DC, Gritsina G, Lauing KL, Giles FJ, Wainwright DA. Molecular Pathways: Targeting IDO1 and Other Tryptophan Dioxygenases for Cancer Immunotherapy. Clin Cancer Res. 2015 Dec 15;21(24):5427-33. doi: 10.1158/1078-0432.CCR-15-0420. Epub 2015 Oct 30. Review. PubMed PMID: 26519060; PubMed Central PMCID: PMC4681601.

13: Vacchelli E, Aranda F, Eggermont A, Sautès-Fridman C, Tartour E, Kennedy EP, Platten M, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology. 2014 Dec 15;3(10):e957994. eCollection 2014 Nov. Review. PubMed PMID: 25941578; PubMed Central PMCID: PMC4292223.

14: 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. PubMed PMID: 20197554.

15: 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. PubMed PMID: 20124451.