S1 Supporting Information Discovery of an Orally Selective Inhibitor of Signal Transducer and Activator of Transcription 3 Using Advanced Multiple Ligand Simultaneous Docking Wenying Yu, Chenglong Li, Wenda Zhang, Yuanzheng Xia, Shanshan Li, Jia-yuh Lin, Keqin Yu, Mu Liu, Lei Yang, Jianguang Luo, Yijun Chen, Hongbin Sun and Lingyi Kong* † State Key Laboratory of Natural Medicines, ‡ Department of Natural Medicinal Chemistry, ∥ Laboratory of Chemical Biology, @ Center for Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. § Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States ⊥ Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland 21201, United States # Water Supply and Drainage, Nanchang Hangkong University, 696 Fenghe Ave. S., Nanchang 330046, China. *Corresponding Author: Phone: +86-25-8327-1405; Fax: +86-25-8327-1405; E-mail: cpu_lykong@126.com Table of contents: 1. Supplementary Design S2–S6 2. Supplementary Biological Assays S7–S11 3. Supplementary PAIN assay S11 4. Methods and Method Validation of Pharmacokinetic Study S11–S15 5. References S16