scholarly journals Screening and In Vitro Testing of Antifolate Inhibitors of Human Cytosolic Serine Hydroxymethyltransferase

ChemMedChem ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 490-497 ◽  
Author(s):  
Alessandro Paiardini ◽  
Alessio Fiascarelli ◽  
Serena Rinaldo ◽  
Frederick Daidone ◽  
Giorgio Giardina ◽  
...  
1967 ◽  
Vol 17 (03/04) ◽  
pp. 405-411
Author(s):  
M Hume

SummaryUrokinase and urokinase-activated plasmin have been given to the dog and rabbit. A thrombolytic state has been induced. Purified urokinase has induced lysis of the experimental radioactive blood clot embolus in the circulation. Demonstration of effectiveness in this animal experiment is hampered by inhibition of the agents in the circulation to a degree much greater than was noted in previous experiments with streptokinase. In vitro testing indicates that under proper conditions urokinase will be an effective agent in the treatment of human thromboembolism.


Oncogene ◽  
2021 ◽  
Author(s):  
Jian Chen ◽  
Risi Na ◽  
Chao Xiao ◽  
Xiao Wang ◽  
Yupeng Wang ◽  
...  

Abstract5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2–p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.


2019 ◽  
Vol 93 ◽  
pp. 25-35 ◽  
Author(s):  
Nicholas N. Ashton ◽  
Gina Allyn ◽  
Scott T. Porter ◽  
Travis J. Haussener ◽  
Paul R. Sebahar ◽  
...  

1984 ◽  
Vol 11 (5) ◽  
pp. 279-282 ◽  
Author(s):  
Robert L. Rietschel ◽  
Ronald Muggins ◽  
Nicole Levy ◽  
Pat M. Pruitt

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