更新于：2024-11-01

MTHFD2 x MTHFD1L

更新于：2024-11-01

基本信息

关联

项与 MTHFD2 x MTHFD1L 相关的药物

TH-9619

靶点

MTHFD1L x MTHFD2

作用机制

MTHFD1L inhibitors [+1]

在研机构

The University of Sheffield [+1]

原研机构

The University of Sheffield [+1]

在研适应症

B细胞恶性肿瘤 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MTHFD2 x MTHFD1L 相关的临床结果

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100 项与 MTHFD2 x MTHFD1L 相关的转化医学

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0 项与 MTHFD2 x MTHFD1L 相关的专利（医药）

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项与 MTHFD2 x MTHFD1L 相关的文献（医药）

2023-12-01·Chemical Biology & Drug Design

Folate trapping is lethal to cancer cells

Article

作者: Rather, Gulam Mohmad

AbstractRegulation of formate flux by a key folate enzyme, MTHFD2 (methylene tetrahydrofolate dehydrogenase 2) in cancer cells remains poorly understood. Green et al. (Nature Metabolism, 2023; 5: 642–659) showed an interesting phenomenon of “folate trapping” toxicity leads to cancer cell kill using a potent inhibitor (TH9619) against the dehydrogenase and cyclohydrolase (DC) activities of cytosolic methylenetetrahydrofolate dehydrogenase 1 (cMTHFD1) and nuclear methylenetetrahydrofolate dehydrogenase 2 (nMTHFD2), but not the mitochondrial MTHFD2 (mTHFD2). But, mMTHFD2 is required for formate flow to cytosol which leads to the trapping of 10‐formyl tetrahydrofolate and causes toxicity by TH9619 treatment, to kill cancer cells expressing mMTHFD2. This article opens new avenues to be evaluated for therapeutic benefits of cancer patients where MTHFD2 shows overexpression viz‐a‐viz breast, prostate, colorectal, acute myeloid leukemia, and other cancer types.

2023-08-09·Nutrients

Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease.

Article

作者: Chen, Qian ; Luo, Manjun ; Wang, Tingting ; Ou, Jun ; Qin, Jiabi ; Chen, Yige ; Liu, Hanjun

Existing evidence supported that congenital heart defect (CHD) was associated with a combination of environmental and genetic factors. Based on this, this study aimed at assessing the association of maternal folic acid supplementation (FAS), genetic variations in offspring methylenetetrahydrofolate dehydrogenase (MTHFD)1 and MTHFD2 genes, and their interactions with CHD and its subtypes. A hospital-based case-control study, including 620 cases with CHD and 620 healthy children, was conducted. This study showed that the absence of FAS was significantly associated with an increased risk of total CHD and its subtypes, such as atrial septal defect (ASD). FAS during the first and second trimesters was associated with a significantly higher risk of CHD in offspring compared to FAS during the three months prior to conception. The polymorphisms of offspring MTHFD1 and MTHFD2 genes at rs2236222, rs11849530, and rs828858 were significantly associated with the risk of CHD. Additionally, a significantly positive interaction between maternal FAS and genetic variation at rs828858 was observed for the risk of CHD. These findings suggested that pregnant women should carefully consider the timing of FAS, and individuals with higher genetic risk may benefit from targeted folic acid supplementation as a preventive measure against CHD.

2022-07-15·Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics

母亲MTHFD1及MTHFD2基因多态性与子代先天性心脏病的关联.

Article

作者: Zhang, Sen-Mao ; Qin, Jia-Bi ; Liu, Yi-Ping ; Wang, Ting-Ting ; Huang, Peng ; Song, Xin-Li ; Chen, Qian ; Sun, Meng-Ting

目的: 探讨母亲亚甲基四氢叶酸脱氢酶（methylenetetrahydrofolate dehydrogenase，MTHFD）1、2（MTHFD1、MTHFD2）基因多态性与子代先天性心脏病（congenital heart disease，CHD）的关联。方法: 采用以医院为基础的病例对照研究，选取2017年11月至2020年3月在湖南省儿童医院就诊的683例单纯CHD患儿的母亲作为病例组，选取同时间段内就诊于同一家医院并排除任何先天畸形的740例儿童的母亲作为对照组。通过问卷调查，收集研究对象的相关暴露信息。完成调查问卷后，采集母亲5 mL静脉血，用于MTHFD1、MTHFD2基因多态性的检测。采用多因素logistic回归模型分析MTHFD1、MTHFD2基因多态性与CHD的关联；采用Haploview 4.2软件的四配子检验法构建单倍型，评估单倍型与CHD的关联；并采用广义多因子降维法和logistic回归法分析基因-基因交互作用与CHD的关联。结果: 多因素logistic回归分析显示，母亲MTHFD1基因rs11849530位点（GA vs AA：OR=1.49；GG vs AA：OR=2.04）和rs1256142位点（GA vs GG：OR=2.34；AA vs GG：OR=3.25）显著增加子代CHD的发生风险（P<0.05），而母亲MTHFD1基因rs1950902位点（AA vs GG：OR=0.57）和MTHFD2基因rs1095966位点（CA vs CC：OR=0.68）显著降低子代CHD的发生风险（P<0.05）。母亲携带单倍型G-G-G（OR=1.86）、G-A-G（OR=1.35）显著增加子代CHD的发生风险（P<0.05）。交互作用分析显示，母亲MTHFD基因2个位点（MTHFD1 rs1950902、MTHFD1 rs2236222）的一阶交互作用及3个位点（MTHFD1 rs1950902、MTHFD1 rs1256142、MTHFD2 rs1095966）的二阶交互作用可能与CHD的发生风险存在关联（P<0.05）。结论: 母亲MTHFD1、MTHFD2基因多态性及其单倍型，以及2个位点（MTHFD1 rs1950902、MTHFD1 rs2236222）和3个位点（MTHFD1 rs1950902、MTHFD1 rs1256142、MTHFD2 rs1095966）的交互作用与子代CHD的发生相关。.