1204669-58-8

Basic information

• Product Name: Epacadostat (INCB024360)
• Synonyms: (Z)-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-[2-(sulfamoylamino)ethylamino]-1,2,5-oxadiazole-3-carboxamidine;Epacadostat(INCN024360);Epacadostat(INCB024360);[C(Z)]-4-[[2-[(Aminosulfonyl)amino]ethyl]amino]-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide;Epacadostat;1,2,5-Oxadiazole-3-carboximidamide, 4-[[2-[(aminosulfonyl)amino]ethyl]amino]-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-, [C(Z)]-;(Z)-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-((2-(sulfamoylamino)ethyl)amino)-1,2,5-oxadiazole-3-carboximidamide;Epacadostat (INCB24360, INCB024360)
• CAS NO: 1204669-58-8
• Molecular Formula: C₁₁H₁₃BrFN₇O₄S
• Molecular Weight: 438.2328232
• Mol File: 1204669-58-8.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 700.9±70.0 °C(Predicted)
• Appearance: /
• Density: 2.01±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to at least 25 mg/ml)
• PKA: 7.65±0.69(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: Epacadostat (INCB024360)(CAS DataBase Reference)
• NIST Chemistry Reference: Epacadostat (INCB024360)(1204669-58-8)
• EPA Substance Registry System: Epacadostat (INCB024360)(1204669-58-8)

Safety Data

• Hazardous Substances Data: 1204669-58-8(Hazardous Substances Data)

Usage

Description

Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1) with an IC50 value of 7.1 nM in HeLa cells that demonstrates little activity against the related enzymes IDO2 or tryptophan 2,3-dioxygenase (TDO). It has been shown to promote T and natural killer-cell growth, to increase IFN-γ production, and to reduce conversion to regulatory T (Treg)-like cells in a coculture system of human allogeneic lymphocytes with either dendritic cells or tumor cells. Epacadostat can also inhibit tumor growth in tumor-bearing mice in a lymphocyte-dependent manner.

Uses

Epacadostat is a potent and novel indoleamine 2,3-dioxygenase (IDO1) inhibitor with IC50 of 10 nM. It has high selectivity over IDO2 and tryptophan 2,3-dioxygenase (TDO).

References

1) Liu?et al.?(2010),?Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity;?Blood?115?3520 2) Koblish?et al.?(2010),?Hydroxyamidine Inhibitors of Indolamine-2,3-dioxygenase Potently Suppress Systemic Tryptophan Catabolism and the Growth of IDO-Expressing Tumors;?Mol. Cancer Ther.?9?489 3) Jochems?et al.?(2016),?The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells;?Oncotarget?7?37762 4) Yentz and Smith (2018),?Indoleamine-2,3-dioxygenase Inhibition as a Strategy to Augment Cancer Immunotherapy;?BioDrugs?32?311 5) Zhu??et al.?(2019),?Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development;?Curr. Oncol. Rep.?21?2 6) Mitchell?et al.?(2018),?Epacadostat Plus Pembrolizumab in Patients with Advanced Solid Tumors: Phase I Results From a Multicenter, Open-Label Phase I/II Trial (ECHO-202/KEYNOTE-037);?J. Clin. Oncol.?36?3223

Upstream product

• 1204669-59-9 4-amino-N‘-hydroxy-N-(2-methoxyethyl)-1,2,5-oxadiazole-3-carboximidamide 
• 1204669-60-2 N¹-hydroxy-4-((2-methoxyethyl)amino)-1,2,5-oxadiazole-3-carboximidamide 
• 1204669-61-3 N-hydroxy-4-[(2-methoxyethyl)amino]-1,2,5-oxadiazole-3-carboximidoyl chloride 
• 1204669-62-4 N-(3-bromo-4-fluorophenyl)-N‘-hydroxy-4-((2-methoxyethyl)amino)-1,2,5-oxadiazole-3-carboximidamide 
• 656-64-4 3-bromo-4-fluoroaniline 
• 914471-43-5 3‐(4‐amino‐1,2,5‐oxadiazol‐3‐yl)‐4‐(3‐bromo‐4‐fluorophenyl)‐1,2,4‐oxadiazol‐5‐one 
• 1771804-78-4 (9H-fluoren-9-yl)methyl N-(2-((4-(4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,2,5-oxadiazol-3-yl)amino)ethyl)sulfamoylcarbamate 
• 1204669-70-4 N-[2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamide 
• 1204669-69-1 (Ν-(2-((4-(4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,2,5-oxadiazol-3-yl)amino)ethyl)tert-butylsulfamoyl)carbamate 
• 1204669-67-9 3‐{4‐[(2‐aminoethyl)amino]‐1,2,5‐oxadiazol‐3‐yl}‐4‐(3‐bromo‐4‐fluorophenyl)‐1,2,4‐oxadiazol‐5‐one hydrochloride 
• 1204669-68-0 tert‐butyl N‐[2‐({4‐[4‐(3‐bromo‐4‐fluorophenyl)‐5‐oxo‐1,2,4‐oxadiazol‐3‐yl]‐1,2,5‐oxadiazol‐3‐yl}amino)ethyl]carbamate 
• 1204669-66-8 3-(4-((2-azidoethyl)amino)-1,2,5-oxadiazole-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazole-5(4H)-one 
• 1204669-65-7 2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl methanesulfonate 
• 1204669-64-6 4-(3-bromo-4-fluorophenyl)-3-{4-[(2-hydroxyethyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-one 

Relevant articles and documents

PROTAC compound for targeted degradation of IDO1, and preparation method and application thereof

The invention provides a PROTAC compound represented by formula I and used for targeted degradation of IDO1, and a pharmaceutically acceptable salt, a hydrate or a solvate thereof. In the formula I, Xrepresents -CH2 or -C = O, Y represents -CH2 or -C= O, and n is a natural number from 2 to 9. The PROTAC compound for targeted degradation of the IDO1 has efficient activity of targeted degradation of the IDO1 protein.

Preparation method of IDO1 inhibitor Epacadostat intermediate

The invention relates to the drug synthesis field, specifically to a preparation method of an IDO1 (indoleamine-2, 3-dioxygenase 1) inhibitor Epacadostat intermediate 4-(3-bromo-4-fluorophenyl)-3-(4-((2-bromoethyl)amino)-1, 2, 5-oxadiazole-3-yl)-1, 2, 4-o

METHOD FOR PREPARING IDO INHIBITOR EPACADOSTAT

Provided is a method for preparing IDO inhibitor epacadostat. The whole reaction route is simple, easy to control and has high yield.