TY - JOUR
T1 - Drug discovery of anticancer drugs targeting methylenetetrahydrofolate dehydrogenase 2
AU - Asai, Ayumu
AU - Koseki, Jun
AU - Konno, Masamitsu
AU - Nishimura, Tatsunori
AU - Gotoh, Noriko
AU - Satoh, Taroh
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Funding Information:
This work was supported partially by grants-in-aid for Scientific Research from the JSPS KAKENHI (grant nos. 17H04282, 17K19698, 16K15615, and 15H05791) and the Extramural Collaborative Research Grant of Cancer Research Institute, Kanazawa University (to A.A.).
Funding Information:
This work was supported partially by grants-in-aid for Scientific Research from the JSPS KAKENHI (grant nos. 17H04282 , 17K19698 , 16K15615 , and 15H05791 ) and the Extramural Collaborative Research Grant of Cancer Research Institute, Kanazawa University (to A.A.).
Publisher Copyright:
© 2018 The Authors
PY - 2018/12
Y1 - 2018/12
N2 - Many anticancer drugs have serious adverse effects; therefore, it is necessary to target features specific to cancer cells to minimize the effects on healthy cells. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was reported to be specifically enhanced in cancer. We confirmed the validity of MTHFD2 as a drug discovery target using clinical data. In addition, we performed in silico screening to design an anticancer drug specifically targeting MTHFD2. Analysis of the clinical data indicated that MTHFD2 was enhanced in most cancers compared with normal tissues, and affected the prognosis in cancer patients. Candidate compounds for MTHFD2 inhibitors were identified using in silico drug discovery techniques, and the important interactions for MTHFD2 binding were determined. In addition, these candidate compounds decreased levels of MTHFD2 metabolites in cancer cells. The findings of the present study may help to develop anticancer drugs targeting MTHFD2, with a view to minimizing the adverse effects of anticancer drugs.
AB - Many anticancer drugs have serious adverse effects; therefore, it is necessary to target features specific to cancer cells to minimize the effects on healthy cells. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was reported to be specifically enhanced in cancer. We confirmed the validity of MTHFD2 as a drug discovery target using clinical data. In addition, we performed in silico screening to design an anticancer drug specifically targeting MTHFD2. Analysis of the clinical data indicated that MTHFD2 was enhanced in most cancers compared with normal tissues, and affected the prognosis in cancer patients. Candidate compounds for MTHFD2 inhibitors were identified using in silico drug discovery techniques, and the important interactions for MTHFD2 binding were determined. In addition, these candidate compounds decreased levels of MTHFD2 metabolites in cancer cells. The findings of the present study may help to develop anticancer drugs targeting MTHFD2, with a view to minimizing the adverse effects of anticancer drugs.
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U2 - 10.1016/j.heliyon.2018.e01021
DO - 10.1016/j.heliyon.2018.e01021
M3 - Article
AN - SCOPUS:85058231816
SN - 2405-8440
VL - 4
JO - Heliyon
JF - Heliyon
IS - 12
M1 - e01021
ER -
