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Updated: Apr 6, 2026

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode
Published on: June 4, 2021
Discovery of Tyk2 inhibitors via the virtual site-directed fragment-based drug design
Woo Dae Jang1, Jun-Tae Kim1, Hoon Young Son2
1Graduate School of New Drug Discovery and Development, Chungnam National University, Daehakno 99, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Abstract:
In this study, we synthesized compound 12 with potent Tyk2 inhibitory activity from FBDD study and carried out a cell-based assay for Tyk2/STAT3 signaling activation upon IFNα5 stimulation. Compound 12 completely suppressed the IFNα5-mediated Tyk2/STAT3 signaling pathway as well as the basal levels of pSTAT3. Stimulation with IFNα/β leads to the tyrosine phosphorylation of the JAK1 and Tyk2 receptor-associated kinases with subsequent STATs activation, transmitting signals from the cell surface receptor to the nucleus. In conclusion, the potency of compound 12 to interrupt the signal transmission of Tyk2/STAT3 appeared to be equivalent or superior to that of the reference compound.
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