Thymidylate synthase (TS) is critical enzyme for the synthesis of DNA- it converts dUMP (2′-deoxyuridine-5′-monophosphate) into dTMP (2′-deoxythymidine-5′-monophosphate). Raltitrexed is an antimetabolite drug used in chemotherapy, and was developed as a direct and specific inhibitor of TS[3]. Raltitrexed (0.5 μg/mL) shows typical apoptotic morphology, including nuclear shrinkage, fragmentation, chromatin condensation and apoptotic bodies in SGC7901 cells. Raltitrexed blocks the cell cycle at the G0/G1 phase, decreases in the mitochondrial membrane potential. Raltitrexed also increases the level of ROS, induces caspase-3-dependent apoptosis via activation of the mitochondria, and increases TS protein and mRNA expression levels[4]. Raltitrexed (1.5 nM) reduces the number of GM00637 cells, selectively induces gene conversions, but does not affect DSB-induced HR or NHEJ[5]. Raltitrexed (0, 5, 10, 11.5, 13.5, 15 mg/kg b/w, i.p.) increases the rates of resorbed embryos and growth retardation of murine model of NTDs in a dose dependent manner. Raltitrexed (11.5 mg/kg b/w) maximally inhibits the thymidylate synthase (TS) activity in embryonic tissue, decreases dTMP levels and while increases dUMP levels[6].
Raltitrexed 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
chinese hamster D4 cells
Proliferation assay
96 h
Antiproliferative activity against chinese hamster D4 cells expressing human FRbeta assessed as reduction of viable cells after 96 hrs, IC50=22 nM
21879757
human HepG2 cells
Cytotoxicity assay
48 h
Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, IC50=1.3 μM
23490159
human IGROV1 cells
Proliferation assay
Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells, IC50=12.6 nM
18680275
human KB cells
Cytotoxicity assay
96 h
Cytotoxicity against human KB cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay, IC50=5.9 nM
Antiproliferative activity against chinese hamster D4 cells expressing human FRbeta assessed as reduction of viable cells after 96 hrs, IC50=22 nM
21879757
human HepG2 cells
Cytotoxicity assay
48 h
Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, IC50=1.3 μM
23490159
human IGROV1 cells
Proliferation assay
Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells, IC50=12.6 nM
18680275
human KB cells
Cytotoxicity assay
96 h
Cytotoxicity against human KB cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay, IC50=5.9 nM
25234128
human KB cells
200 nM
Cytotoxicity assay
96 h
Cytotoxicity against human KB cells assessed as cell growth inhibition incubated up to 96 hrs in presence of 200 nM folic acid by Celltiter-blue cell viability assay, IC50=22 nM
25234128
L1210 cell line
Growth inhibition assay
Growth inhibition of murine tumor L1210 cell line, IC50=9 nM
10508430
L1210 mouse leukemia cells
Function assay
Compound was evaluated for inhibition of thymidylate synthase, partially purified from L1210 mouse leukemia cells that overproduce thymidylate synthase due to amplification of TS gene, Ki=0.418 μM
1372358
MCF7 cells
Cytotoxicity assay
48 h
Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay, IC50=12.6 μM
23490159
PC43-10 cells
Function assay
96 h
Inhibition of RFC (unknown origin) expressed in Chinese hamster PC43-10 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay, IC50=6.3 nM
25234128
R2 cells
Cytotoxicity assay
96 h
Cytotoxicity against chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTitre-Blue fluorescence assay
24256410
R2 cells
Growth inhibition assay
96 h
Growth inhibition of Chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTiter-blue assay, IC50=0.0995 μM
24111942
R2/PCFT4 cells
Function assay
96 h
Inhibition of PCFT (unknown origin) expressed in Chinese hamster R2/PCFT4 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay, IC50=0.0995 μM
25234128
RT16 cells
Proliferation assay
96 h
Antiproliferative activity against chinese hamster RT16 cells expressing human FRalpha assessed as reduction of viable cells after 96 hrs, IC50=15 nM
21879757
SGC7901 cells
Cytotoxicity assay
48 h
Cytotoxicity against human SGC7901 cells after 48 hrs by MTT assay, IC50=8.7 μM
France
... 展开 >> Institut Sainte Catherine
Avignon Cedex 9, France, 84918
Institut de Cancérologie Montpellier
Montpellier Cedex 5, France, 34298
CHRU de Nîmes - Hôpital Universitaire Carémeau
Nîmes, France, 30029
CHRU de Strasbourg - Hôpital de Hautepierre
Strasbourg, France, 67098
CHRU de Toulouse - Hôpital de Rangueil
Toulouse Cedex 9, France, 31059
IUCT-Oncopole
Toulouse, France, 31100 收起 <<
Gastric Cancer
... 展开 >> Peritoneal Carcinomatosis 收起 <<
Phase 3
Not yet recruiting
August 1, 2022
China, Guangdong
... 展开 >>
Department of Abdominal Surgery (Section 2), Affiliated Tumor Hospital of Guangzhou Medical University
Not yet recruiting
Guangzhou, Guangdong, China, 510095
Contact: Xianzi Yang, M.D 8602066673666 7097359@qq.com
Principal Investigator: shuzhong cui, M.D 收起 <<
Italy
... 展开 >> Ospedale Bellaria
Bologna, Italy, I-40139
Istituto Nazionale per la Ricerca sul Cancro
Genoa, Italy, 16132
Istituto Nazionale per lo Studio e la Cura dei Tumori
Naples, Italy, 80131
Universita Degli Studi di Udine
Udine, Italy, 33100
Netherlands
Antoni van Leeuwenhoekhuis
Amsterdam, Netherlands, 1066 CX
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands, 1117 MB 收起 <<
Colorectal Cancer
... 展开 >> Liver Metastasis 收起 <<
Phase 3
Recruiting
September 2018
China, Guangdong
... 展开 >>
The Affiliated Tumor Hospital of Zhongshan University
Not yet recruiting
Guangzhou, Guangdong, China, 510060
Principal Investigator: Zhi-Zhong Pan, MD/PHD
China, Hubei
Wuhan Union Hospital
Not yet recruiting
Wuhan, Hubei, China, 430022
Principal Investigator: Kai-Xiong Tao, MD/PHD
Zhongnan Hospital Affiliated to Wuhan University
Not yet recruiting
Wuhan, Hubei, China, 430071
Principal Investigator: Bing Xiong, MD
China, Shanghai
Changhai Hospital of Shanghai
Recruiting
Shanghai, Shanghai, China, 200433
Principal Investigator: Wei Zhang, MD
China, Zhejiang
The First Affiliated Hospital of College of Medicine Zhejiang University
Not yet recruiting
Hangzhou, Zhejiang, China, 310003
Principal Investigator: Jianjiang Lin, M.D.
Second Affiliated Hospitalof Zhejiang University School of Medicine
Recruiting
Hangzhou, Zhejiang, China, 310009
Contact: Ke-Feng Ding, PhD/MD 86-571-87784827 dingkefeng@zju.edu.cn
Principal Investigator: Ke-Feng Ding, PhD/MD
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Recruiting
Hangzhou, Zhejiang, China, 310016
Principal Investigator: Xuefeng Huang, M.D.
Jinhua People's Hospital
Recruiting
Jinhua, Zhejiang, China, 321000
Principal Investigator: Jinlin Du, M.D.
The second hospital of Ningbo City
Recruiting
Ningbo, Zhejiang, China, 315010
Principal Investigator: Xiao-Yu Dai, MD 收起 <<
Spain
... 展开 >> Research Site
A Coruna, Spain
Research Site
Barcelona, Spain
Research Site
Burgos, Spain
Research Site
Gijon, Spain
Research Site
Leon, Spain
Research Site
Madrid, Spain
Research Site
Oviedo, Spain
Research Site
Pamplona, Spain
Research Site
Valladolid, Spain 收起 <<
China, Beijing
... 展开 >> Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Recruiting
Beijing, Beijing, China, 100021
Contact: Wenyang Liu, MD liuwenyang26@163.com 收起 <<
China, Liaoning
... 展开 >>
The First Hospital of China Medical University
Recruiting
Shenyang, Liaoning, China, 110001
Contact: Yunpeng Liu, MD., PhD 86-24-83282312 cmuliuyunpeng@hotmail.com
Principal Investigator: Yunpeng Liu, MD., PhD. 收起 <<
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