TY - GEN
T1 - Screening of sonic hedgehog (Shh) inhibitors in the hedgehog signaling pathway from traditional chinese medicine (TCM) database through structure-based pharmacophore design
AU - Rizki, Ilmi Fadhilah
AU - Nasution, Mochammad Arfin Fardiansyah
AU - Siregar, Syafrida
AU - Ekawati, Mega Maulina
AU - Tambunan, Usman Sumo Friend
N1 - Publisher Copyright:
© Springer International Publishing AG, part of Springer Nature 2018.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - Sonic hedgehog
KW - Structure-Based pharmacophore design
KW - Traditional Chinese Medicine
UR - http://www.scopus.com/inward/record.url?scp=85050334464&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-94968-0_16
DO - 10.1007/978-3-319-94968-0_16
M3 - Conference contribution
AN - SCOPUS:85050334464
SN - 9783319949673
T3 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
SP - 179
EP - 184
BT - Bioinformatics Research and Applications - 14th International Symposium, ISBRA 2018, Proceedings
A2 - Zhang, Fa
A2 - Zhang, Shihua
A2 - Cai, Zhipeng
A2 - Skums, Pavel
PB - Springer Verlag
T2 - 14th International Symposium on Bioinformatics Research and Applications, ISBRA 2018
Y2 - 8 June 2018 through 11 June 2018
ER -