163239-22-3

Basic information

• Product Name: 680C91
• Synonyms: 680C91;1H-Indole, 6-fluoro-3-[(1E)-2-(3-pyridinyl)ethenyl]-;6-Fluoro-3-[(1E)-2-(3-pyridinyl)ethenyl)-1H-indole
• CAS NO: 163239-22-3
• Molecular Formula: C15H11FN2
• Molecular Weight: 238.2596432
• Mol File: 163239-22-3.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 431.2±35.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.305±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥10mg/mL
• PKA: 15.92±0.30(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
• CAS DataBase Reference: 680C91(CAS DataBase Reference)
• NIST Chemistry Reference: 680C91(163239-22-3)
• EPA Substance Registry System: 680C91(163239-22-3)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-39
• WGK Germany: 3
• Hazardous Substances Data: 163239-22-3(Hazardous Substances Data)

Usage

Description

680C91 (163239-22-3) is a potent and selective inhibitor of tryptophan 2,3-dioxygenase (TDO) Ki=42 nM).1,2?Displays no activity against indoleamine 2,3-dioxygenase, MAO-A and B and does not effect serotonin uptake. Elevates CSF tryptophan by up to 260% and CSF serotonin by 170% of basal.2?TDO inhibition by 680C91 in glioma cells blocked the release of kynurenine (Cat.# 10-2666), an endogenous tumor promoting AHR ligand.4

Uses

680C91 has been used:as a tryptophan 2,3 dioxygenase (TDO) inhibitor to study its effects on the pigmentation in Doryteuthis pealeii embryosas a TDO inhibitor to study its effects on esophageal squamous cell carcinoma in xenograft tumor assayas a tryptophan 2,3 dioxygenase 2 (TDO2) inhibitor to study its effects on toxic fragment formation in human embryonic kidney cells

Definition

ChEBI: A fluoroindole that is 6-fluoroindole in which the hydrogen at position 3 has been replaced by a 2-(pyridin-3-yl)vinyl group (trans configuration). It is a selective inhibitor of tryptophan 2,3-dioxygenase (TDO), which directs the conversi n of trypophan to kynurenin.

Biochem/physiol Actions

680C91 is a potent inhibitor of the enzyme tryptophan 2,3-dioxygenase (TDO), which directs the conversion of trypophan to kynurenin. Kynurenin has recently been identified as an endogenous lignd of the arylhydrocarbon receptor (AHR). TDO is highly expressed in glioma cells, and contributes to AHR-mediated glioma cell survival and suppression of anti-tumor immune responses.

References

1) Schwarcz and Pellicciari (2002),?Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities; J. Pharmacol. Exp. Therap.,?303?1 2) Salter?et al. (1995),?The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism; Biochem. Pharmacol,?49?1435 3) Salter?et al. (1995),?The effects of an inhibitor of tryptophan 2,3-dioxygenase and a combined inhibitor of tryptophan 2,3-dioxygenase and 5-HT reuptake in the rat; Neuropharmacology,?34?217 4) Opitz?et al. (2011),?An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor; Nature,?478197

Upstream product

• 2795-41-7 6-fluoro-1H-indole-3-carbaldehyde 
• 6419-36-9 3-pyridineacetic acid hydrochloride 
• 446-10-6 2-nitro-4-fluorotoluene 
• 399-51-9 6-fluoro-1H-indole 
• 96631-90-2 N,N-dimethyl-2-(4-fluoro-2-nitrophenyl)ethenylamine 
• 501-81-5 pyridyl-3-yl-acetic acid 

Relevant articles and documents

Novel tryptophan dioxygenase inhibitors and combined tryptophan dioxygenase/5-HT reuptake inhibitors

Tryptophan dioxygenase (TDO) is a liver enzyme that is responsible for the majority of the metabolism of tryptophan. A series of novel 3-(2-pyridylethenyl)indoles are shown to be potent inhibitors of TDO with selected members of the series also having 5-hydroxy tryptamine (5-HT) reuptake inhibitory activity. These compounds are shown to provide significant increases in the levels of tryptophan and 5-HT in the cerebrospinal fluid and are thus of interest for antidepressant therapy.

Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators

Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure-activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His55 and Thr254 residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (Ki = 5.5 μM), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.