Pharmacophore-Based Virtual Screening and Experimental Validation of Pyrazolone-Derived Inhibitors toward Janus Kinases.

ABSTRACT: Janus kinases (JAKs) are nonreceptor protein tyrosine kinases that play a role in a broad range of cell signaling. JAK2 and JAK3 have been involved in the pathogenesis of common lymphoid-derived diseases and leukemia cancer. Thus, inhibition of both JAK2 and JAK3 can be a potent strategy to reduce the risk of these diseases. In the present study, the pharmacophore models built based on the commercial drug tofacitinib and the JAK2/3 proteins derived from molecular dynamics (MD) trajectories were employed to search for a dual potent JAK2/3 inhibitor by a pharmacophore-based virtual screening of 54 synthesized pyrazolone derivatives from an in-house data set. Twelve selected compounds from the virtual screening procedure were then tested for their inhibitory potency against both JAKs in the k

SUBMITTER: Sanachai K 

PROVIDER: S-EPMC9494641 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature