Nagarajan, Shanthi Choo, Hyunah Cho, Yong Seo Oh, Kwang-Seok Lee, Byung Ho Shin, Kye Jung Pae, Ae Nim 2024-01-20T19:03:10Z 2024-01-20T19:03:10Z 2021-09-02 2010-06-01 0968-0896 https://pubs.kist.re.kr/handle/201004/131343 I kappa B kinase (IKK) is critical in proinflammatory cytokine-induced I kappa B alpha phosphorylation and subsequent activation of the nuclear transcription factor NF-kappa B complex. The activated NF-kappa B plays a major role in the pathogenesis of a number of human disorders, such as rheumatic and chronic inflammatory diseases. The inhibition of NF-kappa B activation by small molecule inhibitors that targets IKK beta may provide a pharmacological basis for interfering with these acute processes. To date, only three inhibitors have passed preclinical trials; on the other hand, identifying novel IKK beta inhibitors could evolve as potential candidates to meet the clinical requirements in the future. In the present work, we have employed a virtual screening (VS) method to identify novel compounds. The VS scheme is comprised of pharmacophore filtering and, subsequently, receptor based screening. The VS scheme was applied to the databases of 1.04 million compounds to identify three novel compounds that can inhibit the IKK beta at a micro molar range. Moreover, these compounds can be raised into a potential anti-inflammatory drug candidate after optimizing and passing several phases of clinical trials. (C) 2010 Published by Elsevier Ltd. English PERGAMON-ELSEVIER SCIENCE LTD NF-KAPPA-B PROTEIN-KINASE-A ANTICANCER AGENT IN-VITRO DISCOVERY DESIGN POTENT CHS-828 CYANOGUANIDINE INFLAMMATION IKK beta inhibitors identification part II: Ligand and structure-based virtual screening Article 10.1016/j.bmc.2010.04.030 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.18, no.11, pp.3951 - 3960 BIOORGANIC & MEDICINAL CHEMISTRY 18 11 3951 3960 scie scopus 000278078600036 2-s2.0-77953133638 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article NF-KAPPA-B PROTEIN-KINASE-A ANTICANCER AGENT IN-VITRO DISCOVERY DESIGN POTENT CHS-828 CYANOGUANIDINE INFLAMMATION IkappaB kinase (IKK) IKK beta Homology modeling Virtual screening Pharmacophore Docking