Title :

Rational Design of Original Fused-Cycle Selective Inhibitors of Tryptophan 2,3-Dioxygenase.

Author(s) :

Kozlova, A. [Auteur]
Thabault, L. [Auteur]
Liberelle, Maxime [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Klaessens, S. [Auteur]
Prévost, J. R. C. [Auteur]
Mathieu, C. [Auteur]
Pilotte, L. [Auteur]
Stroobant, V. [Auteur]
Van Den Eynde, B. [Auteur]
Frédérick, R. [Auteur]

Journal title :

Journal of Medicinal Chemistry

Volume number :

64

Pages :

10967–10980

Publication date :

2021-08-08

ISSN :

1520-4804

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Tryptophan 2,3-dioxygenase (TDO2) is a heme-containing enzyme constitutively expressed at high concentrations in the liver and responsible for l-tryptophan (l-Trp) homeostasis. Expression of TDO2 in cancer cells results ...
Show more >Tryptophan 2,3-dioxygenase (TDO2) is a heme-containing enzyme constitutively expressed at high concentrations in the liver and responsible for l-tryptophan (l-Trp) homeostasis. Expression of TDO2 in cancer cells results in the inhibition of immune-mediated tumor rejection due to an enhancement of l-Trp catabolism via the kynurenine pathway. In the study herein, we disclose a new 6-(1H-indol-3-yl)-benzotriazole scaffold of TDO2 inhibitors developed through rational design, starting from existing inhibitors. Rigidification of the initial scaffold led to the synthesis of stable compounds displaying a nanomolar cellular potency and a better understanding of the structural modulations that can be accommodated inside the active site of hTDO2.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-01-16T01:56:56Z
2024-06-10T07:18:13Z