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 (INCB024360) is a potent and selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with an IC50 value of 7.1 nM in HeLa cells. It demonstrates high selectivity over IDO2 and tryptophan 2,3-dioxygenase (TDO) and has been shown to promote T and natural killer-cell growth, increase IFN-γ production, and reduce the 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

Used in Oncology:
Epacadostat (INCB024360) is used as an anticancer agent for its ability to inhibit the IDO1 enzyme, which is often overexpressed in various cancers. By targeting IDO1, Epacadostat can modulate the tumor microenvironment, enhance the immune system's response against cancer cells, and potentially improve the efficacy of other cancer treatments.
Used in Immuno-Oncology:
Epacadostat (INCB024360) is used as an immunomodulatory agent for its ability to promote T and natural killer-cell growth, increase IFN-γ production, and reduce the conversion to regulatory T (Treg)-like cells. This can help enhance the immune system's ability to recognize and attack cancer cells, making it a valuable component in the development of novel immuno-oncology therapies.
Used in Drug Combinations:
Epacadostat (INCB024360) is used as a combination therapy agent for its potential to enhance the chemo-sensitivity and efficacy of conventional chemotherapeutic drugs in resistant cases. By inhibiting the IDO1 enzyme, Epacadostat may help overcome resistance to chemotherapy and improve overall treatment outcomes for cancer patients.

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

• 1204669-69-1 (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 
• 1204669-63-5 4-(3-bromo-4-fluorophenyl)-3-{4-[(2-methoxyethyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-one 
• 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 
• 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 
• 1204669-66-8 3-(4-((2-azidoethyl)amino)-1,2,5-oxadiazole-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazole-5(4H)-one 
• 1204669-68-0 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 
• 1204669-67-9 3‐{4‐[(2‐aminoethyl)amino]‐1,2,5‐oxadiazol‐3‐yl}‐4‐(3‐bromo‐4‐fluorophenyl)‐1,2,4‐oxadiazol‐5‐one hydrochloride 
• 1204669-70-4 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 
• 1204669-59-9 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 
• 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 
• 914471-43-5 3‐(4‐amino‐1,2,5‐oxadiazol‐3‐yl)‐4‐(3‐bromo‐4‐fluorophenyl)‐1,2,4‐oxadiazol‐5‐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

Synthetic method of IDO inhibitor Aikaduosita

The invention discloses a synthetic method of an IDO inhibitor Aikaduosita, and relates to the technical field of organic synthesis. The method comprises the following steps: carrying out an addition rearrangement reaction on N-Boc-ethylene diamine used as a raw material to obtain an intermediate 1, carrying out an acid deprotection reaction on the intermediate 1 to obtain an intermediate 2, carrying out a condensation reaction on the intermediate 2 and a compound 1 to obtain an intermediate 3, and carrying out an alkaline ring opening reaction on the intermediate 3 to finally prepare the IDO inhibitor Aikaduosita. Compared with reported methods, the method disclosed in the invention has the advantages of short route, high yield, simplicity in post-treatment, avoiding of explosive reagents and ultralow temperature conditions, small pollution, and suitableness for industrial production.