LY 345899 is a Folate analog and is a methylene tetrahydrofolate dehydrogenase (MTHFD1; DC301) and MTHFD2 inbhibitor with IC50 values of 96 nM and 663 nM, respectively and a Ki of 18 nM for MTHFD1.
LY 345899 could suppress the MTHFD enzyme in the cytoplasm and mitochondria.
LY 345899 could disturb the NADPH and redox homeostases and accelerate cell death under oxidative stress, such as hypoxia, or causing in vitro anchorage independence and in vivo impaired tumor growth and metastasis.
体内研究
LY345899 (Intraperitoneal injection; 5-10 mg/kg; 5 d/wk; 4 weeks) shows potent antitumor activity and displays therapeutic activity against CRC in vivo.
Animal Model:
SW620 or PDX-based BABL/c nude colorectal cancer (CRC) model
Displayed lower cell proliferation indices and higher cell apoptosis. Exhibited no statistically significant weight loss or other signs of acute or delayed toxicity in mice.
分子式
C20H21N7O7
分子量
471.42
CAS号
10538-99-5
运输条件
Room temperature in continental US; may vary elsewhere.