QL-1200186

QL-1200186 is a selective, orally active, allosteric inhibitor targeting the tyrosine kinase TYK2 pseudokinase domain JH2 (IC50=0.06 nM, TYK2 JH2), with 164-fold selectivity over TYK1 JH2 (IC50=9.85 nM, TYK1 JH2) . QL-1200186 first stabilizes the TYK2 JH2 conformation, inhibits the activity of the JH1 catalytic domain, and blocks the IFNα, IL-12/IL-23-mediated JAK-STAT signaling pathway. QL-1200186 can inhibit the production of Th1/Th17 cell-related cytokines (such as IFNγ, IL-23), reduce immune cell activation, and has no significant effect on JAK1/2/3 kinase activity. QL-1200186 can significantly improve skin inflammation in the Imiquimod (HY-B0180) -induced psoriasis mouse model and reduce the Psoriasis Area and Severity Index (PASI) score. QL-1200186 can be used in the study of autoimmune diseases such as psoriasis and systemic lupus erythematosus (SLE) [1].

Product Specifications

CAS Number

[2848664-42-4]

UNSPSC

12352005

Target

IFNAR; Interleukin Related; STAT

Type

Reference compound

Related Pathways

Immunology/Inflammation; JAK/STAT Signaling; Stem Cell/Wnt

Applications

COVID-19-immunoregulation

Field of Research

Inflammation/Immunology

Assay Protocol

https://www.medchemexpress.com/ql-1200186.html

Purity

99.95

Solubility

DMSO : 100 mg/mL (ultrasonic)

Smiles

COC(C(C(C=C1)=NN1C)=CC(CCOCC2=NC3=CC=C2)=C4)=C4NC(C=C(N3)N=C5)=C5C(NC)=O

Molecular Formula

C26H27N7O3

Molecular Weight

485.54

References & Citations

[1]Chen CX, et al. A novel highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2) can block inflammation-and autoimmune-related pathways. Cell Commun Signal. 2023;21 (1) :287. Published 2023 Oct 16.