Drugs of the future: CBLB502

A chunk of Salmonella flagellum has been shown to protect mice and rhesus monkeys from the toxic effects of ionizing radiation. The drug binds to Toll-like receptor 5 (TLR5) and turns on the nuclear factor-κB signaling pathway, which leads to the induction of factors that protect cells (apoptosis inhibitors and reactive oxygen species scavengers) and promote tissue regeneration (cytokines). The activation of this pathway also results in the inhibition of the p53 tumour suppressor pathway, which is one of the means by which cancer cells are able to resist the effects of radiation. Incidentally, things like cytokines and amifostine are also radioprotective, but CBLB502 appears to be the best of 'em.

Flagellin, the principal protein component of bacterial flagella, is the only thing that we know of that binds to and activates TLR5. The drug was synthesized based on the structure of flagellin made by Salmonella enterica serovar Dublin, a human pathogen found in raw cow milk.

A single injection of CBLB502 was able to protect mice from the normally lethal whole-body gamma-radiation doses of 10 and 13 Gy, and increased their survival by almost a week after a dose of 17 Gy.

If this is legit, it could mean safer cancer radiotherapy and better protection in radiation emergencies.

Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman AS, Gupta D, Kurnasov OV, Fort FL, Osterman AL, Didonato JA, Feinstein E, Gudkov AV. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science. 2008 Apr 11;320(5873):226-30.

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