Pharmacophore-Based Virtual Screening and Experimental Validation of Pyrazolone-Derived Inhibitors toward Janus Kinases
Kamonpan Sanachai, Panupong Mahalapbutr, Kowit Hengphasatporn, Yasuteru Shigeta, Supaphorn Seetaha, Lueacha Tabtimmai, Thierry Langer, Peter Wolschann, Tanakorn Kittikool, Sirilata Yotphan, Kiattawee Choowongkomon, Thanyada Rungrotmongkol
Abstract
) value of 12.61 nM for JAK2 and 15.80 nM for JAK3. From the MD simulations study, it could be found that the sulfonamide group of TK4g can form hydrogen bonds in the hinge region at residues E930 and L932 of JAK2 and E903 and L905 of JAK3, while van der Waals interaction also plays a dominant role in ligand binding. Altogether, TK4g, found by virtual screening and biological tests, could serve as a novel therapeutical lead candidate.
Topics & Concepts
PharmacophoreVirtual screeningJanus kinaseKinaseJanus kinase 2Janus kinase 3ChemistryIC50Tyrosine kinasePyrazolonePharmacologyCancer researchBiochemistryComputational biologyIn vitroBiologySignal transductionCytotoxic T cellAntigen-presenting cellCytokine Signaling Pathways and InteractionsMyeloproliferative Neoplasms: Diagnosis and Treatment