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news.Pralatrexate has shown efficacy with less toxicity than other therapeutic regimens and is being studied against several forms of cancer
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The FDA has approved pralatrexate for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Research on drugs of this class began in the 1950s at SRI International. It is a collaboration among SRI International, Memorial Sloan-Kettering Cancer Center, and Southern Research Institute. It led to clinical trials on related compounds conducted by Memorial Sloan-Kettering Cancer Center starting in the 1980s. Pralatrexate was identified as a viable clinical candidate and was licensed to Allos Therapeutics for further development in 2002, said the comapny.
Pralatrexate has shown efficacy with less toxicity than other therapeutic regimens and is being studied against several forms of cancer, including peripheral T-cell lymphoma and non-small-cell lung cancer.
The drug is a selective antifolate designed to accumulate preferentially in cancer cells. Based on preclinical studies, Allos believes that pralatrexate selectively enters cells expressing RFC-1, a protein that is over expressed on certain cancer cells compared to normal cells. Once inside cancer cells, pralatrexate is efficiently polyglutamylated, which leads to high intracellular drug retention.
Polyglutamylated pralatrexate essentially becomes ‘trapped’ inside cancer cells, making it less susceptible to efflux-based drug resistance. Acting on the folate pathway, pralatrexate interferes with DNA synthesis and triggers cancer cell death.
Francis Sirotnak, one of the inventors of pralatrexate and a molecular pharmacologist and Memorial Sloan-Kettering Cancer Center Member Emeritus, said: “In the laboratory and in clinical trials at Sloan-Kettering, we were able to demonstrate that this was a therapeutically active drug. After many years of research and drug development, it is very rewarding to see this work come to fruition.”
Joseph DeGraw and William Colwell of SRI International, said: “We are pleased that our long-term medicinal chemistry program in the area of antifolate therapeutic agents has resulted in development of a clinically effective drug for treatment of certain types of human cancer. This was achieved through SRI’s long-standing collaboration with the chemistry and molecular therapeutics investigators at Southern Research Institute and Memorial Sloan-Kettering Cancer Center.”