1.Scaffold and SAR studies on c-MET inhibitors using machine learning approaches.
Jing ZHANG ; Mingming ZHANG ; Weiran HUANG ; Changjie LIANG ; Wei XU ; Jinghua ZHANG ; Jun TU ; Innocent Okohi AGIDA ; Jinke CHENG ; Dong-Qing WEI ; Buyong MA ; Yanjing WANG ; Hongsheng TAN
Journal of Pharmaceutical Analysis 2025;15(6):101303-101303
Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC50) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.
2.Epidemiological characteristics and prevention strategy of Japanese encephalitis from 2003 to 2012 in Shaoguan
Liang XU ; Jianhong TANG ; Canlin QIU ; Ziqiang XU ; Changjie LI
International Journal of Laboratory Medicine 2014;(8):1001-1002
Objective Through the 2003 -2012 epidemic encephalitis B cases analysis ,to study the prevalence of epidemic en-cephalitis B in Shaoguan ,and to provide the scientific basis for the prevention and control epidemic encephalitis B .Methods Active surveillance of suspected cases ,retrospective analysis of laboratory confirmed cases related materials were done .Results There were 47 cases who suffered from epidemic encephalitis B in Shaoguan from 2003 to 2012 ,and 2 death cases occurred .Epidemic en-cephalitis B incidence in years was (0 -0 .531) /10 million .There was a morbidity peak in June and July ,which accounted for 87 .23% of the total incidence ,20 cases occurred in June(42 .55% )and 21 cases occurred in July(44 .68% ) .Men suspected cases in 130 cases ,31 laboratory confirmed cases .Women suspected cases in 86 cases ,16 laboratory confirmed cases .The positive cases of male was more than female .In 47 epidemic encephalitis B cases ,0- <4 years old 6 cases ,4- <7 years old 22 cases ,7- <20 years old 17 cases ,≥ 20 years old 2 cases .Most of the patients were preschool children and students ,accounting for 82 .97% .There were 32 cases with no or uncertain history of vaccination ,accounting for 68 .08% of the total cases .15 cases had history of immunity ,ac-counting for 31 .92% of the total cases .Conclusion Prevention of epidemic encephalitis B should pay more attention to epidemic en-cephalitis B vaccination .Mosquito control work of rural and peri-urban areas should be strengthened .

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