Nagarajan, Shanthi Ahmed, Asif Choo, Hyunah Cho, Yong Seo Oh, Kwang-Seok Lee, Byung Ho Shin, Kye Jung Pae, Ae Nim 2024-01-20T17:34:29Z 2024-01-20T17:34:29Z 2021-09-02 2011-02 1610-2940 https://pubs.kist.re.kr/handle/201004/130694 The inhibitor kappaB kinase beta (IKK beta) is a serine-threonine protein kinase that is critically involved in the activation of the transcription factor nuclear factor kappa B (NF-kappa B) in response to various inflammatory stimuli. IKK beta-selective inhibitors could prove useful for the treatment of inflammatory diseases. In the absence of structural information, a ligand-based approach can serve as an alternative to the virtual screening of large databases. We have developed a 3D QSAR pharmacophore model based on 23 IKK beta inhibitors with 3 nM <= IC50 <= 50000 nM. A four-feature pharmacophore containing a hydrophobic (Hy) feature, two ring aromatic (RA) features, and a hydrogen bond donor (D) feature was constructed. It yielded a correlation coefficient of 0.93 with experimentally determined activity data, and a correlation coefficient of 0.77 with training set activity data. The best hypothesis, Hypo 1, was validated by estimating the activities of 136 compounds in a test set. As well as the correlation analysis and test set activity estimation, a Fisher&apos;s validation test was conducted at the 95% confidence level. The pharmacophore model&apos;s specificity and selectivity were determined in an exhaustive enrichment study. English SPRINGER KAPPA-B KINASE HIT-TO-LEAD CONFORMATIONAL COVERAGE RECEPTOR POTENT DERIVATIVES GENERATION DISCOVERY 3D QSAR pharmacophore model based on diverse IKK beta inhibitors Article 10.1007/s00894-010-0714-8 1 JOURNAL OF MOLECULAR MODELING, v.17, no.2, pp.209 - 218 JOURNAL OF MOLECULAR MODELING 17 2 209 218 scie scopus 000286667800001 2-s2.0-79551596210 Biochemistry & Molecular Biology Biophysics Chemistry, Multidisciplinary Computer Science, Interdisciplinary Applications Biochemistry & Molecular Biology Biophysics Chemistry Computer Science Article KAPPA-B KINASE HIT-TO-LEAD CONFORMATIONAL COVERAGE RECEPTOR POTENT DERIVATIVES GENERATION DISCOVERY IKK Inhibitor kappa B kinase Pharmacophore HypoGen Virtual screening Enrichment