Screening of Sonic Hedgehog (Shh) Inhibitors in the Hedgehog Signaling Pathway from Traditional Chinese Medicine (TCM) Database Through Structure-Based Pharmacophore Design
Colorectal cancer (CRC) is the second most death-leading cancer in the world. The development of CRC is closely related to the hedgehog signaling pathway. The abnormal activation of the pathway will initiate the binding of Sonic Hedgehog (Shh) to Ptch1 that can trigger the growth of abnormal cells that cause CRC. Traditional Chinese Medicine (TCM) compounds were used to inhibit Shh through structure-based pharmacophore design. This research was started by finding the pharmacophore feature of Shh, continued with docking simulation of Shh with TCM compounds. The best three TCM compounds, which are TCM-8941, TCM-28794 and TCM-32808, give the best ligand interaction and have the lowest Gibbs free binding energy. They also have good pharmacological properties that have been analyzed by using Toxtree v2.6.13, SwissADME and admetSAR. For further research, these TCM compounds may be used as drug candidates in colorectal cancer.
KeywordsSonic hedgehog Colorectal cancer Traditional Chinese Medicine Structure-Based pharmacophore design
This research is financially supported by the Directorate of Research and Community Engagement of Universitas Indonesia (DRPM UI) through Hibah Publikasi Internasional Terindeks Untuk Tugas Akhir Mahasiswa (PITTA) UI 2327/UN2.R3.1/HKP.05.00/2018. Herewith, the authors declare that there is no conflict of interest regarding of the manuscript.
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