Discovery of JAK2/3 Inhibitors from Quinoxalinone-Containing Compounds
Kamonpan Sanachai, Panupong Mahalapbutr, Lueacha Tabtimmai, Supaphorn Seetaha, Tanakorn Kittikool, Sirilata Yotphan, Kiattawee Choowongkomon, Thanyada Rungrotmongkol
Abstract
of 17.90 ± 1.36 μM), similar to both tofacitinib ruxolitinib. Mechanistically, ST4j inhibited JAK2 autophosphorylation and induced cell apoptosis in dose- and time-dependent manners. From molecular dynamics simulations, ST4j was mainly stabilized by van der Waals interactions, and its hydroxyl group could form hydrogen bonds in the hinge region at residues S936 and R938 of JAK2. This research highlights the potential of ST4j to be a novel therapeutic agent for the treatment of lymphoid-derived diseases and leukemia cancer.
Topics & Concepts
RuxolitinibTofacitinibAutophosphorylationIC50Janus kinase 2ChemistryApoptosisJanus kinaseDocking (animal)Cancer researchSignal transductionPharmacologyBiochemistryKinaseBiologyIn vitroMedicineImmunologyMyelofibrosisProtein kinase ARheumatoid arthritisBone marrowNursingCytokine Signaling Pathways and InteractionsLymphoma Diagnosis and TreatmentImmune Cell Function and Interaction