Drug discovery of anticancer drugs targeting methylenetetrahydrofolate dehydrogenase 2

被引：25

作者：

Asai, Ayumu ^{[1
,2
,3
]}

Koseki, Jun ^{[1
]}

Konno, Masamitsu ^{[2
]}

Nishimura, Tatsunori ^{[4
]}

Gotoh, Noriko ^{[4
]}

Satoh, Taroh ^{[2
]}

Doki, Yuichiro ^{[1
,2
,3
]}

Mori, Masaki ^{[1
,2
,3
,5
]}

Ishii, Hideshi ^{[1
,2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Med Data Sci, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Frontier Sci Canc & Chemotherapy, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, Suita, Osaka 5650871, Japan

[4] Kanazawa Univ, Canc Res Inst, Div Canc Cell Biol, Kanazawa, Ishikawa 9201192, Japan

[5] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka, Fukuoka 8128582, Japan

来源：

HELIYON | 2018年 / 4卷 / 12期

关键词：

Cancer research; Pharmaceutical science; Molecular biology;

D O I：

10.1016/j.heliyon.2018.e01021

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

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