Tyk2 Targeting in Immune-Mediated Inflammatory Diseases
Rusiñol, Lluís (Universitat Autònoma de Barcelona)
Puig Sanz, Lluís (Institut de Recerca Sant Pau)

Data:	2023
Resum:	The Janus kinase (Jak)/signal transducer and activating protein (STAT) pathways mediate the intracellular signaling of cytokines in a wide spectrum of cellular processes. They participate in physiologic and inflammatory cascades and have become a major focus of research, yielding novel therapies for immune-mediated inflammatory diseases (IMID). Genetic linkage has related dysfunction of Tyrosine kinase 2 (Tyk2)-the first member of the Jak family that was described-to protection from psoriasis. Furthermore, Tyk2 dysfunction has been related to IMID prevention, without increasing the risk of serious infections; thus, Tyk2 inhibition has been established as a promising therapeutic target, with multiple Tyk2 inhibitors under development. Most of them are orthosteric inhibitors, impeding adenosine triphosphate (ATP) binding to the JH1 catalytic domain-which is highly conserved across tyrosine kinases-and are not completely selective. Deucravacitinib is an allosteric inhibitor that binds to the pseudokinase JH2 (regulatory) domain of Tyk2; this unique mechanism determines greater selectivity and a reduced risk of adverse events. In September 2022, deucravacitinib became the first Tyk2 inhibitor approved for the treatment of moderate-to-severe psoriasis. A bright future can be expected for Tyk2 inhibitors, with newer drugs and more indications to come.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Matèria:	Inflammatory diseases ; Psoriasis ; Treatment
Publicat a:	International journal of molecular sciences, Vol. 24 (february 2023) , ISSN 1422-0067

DOI: 10.3390/ijms24043391
PMID: 36834806

17 p, 2.5 MB

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