Premium
Identification of new NIK inhibitors by discriminatory analysis‐based molecular docking and biological evaluation
Author(s) -
Cheng Gang,
Mei XiaoBing,
Yan YouYou,
Chen Jing,
Zhang Bo,
Li Jia,
Dong XiaoWu,
Lin NengMing,
Zhou YuBo
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800374
Subject(s) - docking (animal) , chemistry , identification (biology) , computational biology , combinatorial chemistry , biology , medicine , nursing , botany
NF‐κB inducing kinase (NIK) is a key regulator in the noncanonical nuclear factor κB cells (NF‐κB) signaling pathway. Dysregulation of NIK is often related with autoimmune disorders and malignancies. However, the number of reported NIK inhibitors is scarce. Discriminatory analysis‐based molecular docking was used to examine the accuracy of the binding conformation and to estimate the binding affinity, leading to the identication of several new NIK inhibitors with moderate IC 50 (ranging from 48.9 to 103.4 μM). Among them, compound 5 , the most potent one (IC 50 48.9 ± 6.9 μM), also showed moderate antiproliferation activity against cancer SW1990 cells, with an IC 50 value of 20.1 ± 6.0 μM. Further dynamic simulations were performed to provide more in‐depth details on the binding conformation of compound 5 and the NIK protein, providing some structural clues for further optimization of compound 5 as a novel NIK inhibitor.