Therapeutics: Leukotriene C4 (LTC4); cysteinyl leukotriene receptor 2 (CYSLTR2; CysLT2); CysLT1

Cell culture and mouse studies suggest inhibiting LTC4 or its receptors, CysLT1 and CYSLTR2, could help treat chemotherapy-related toxicity. In a HeLa-derived cell line, the generic chemotherapies doxorubicin and 5-fluorouracil (5-FU) increased levels of LTC4, CysLT1 and CYSLTR2, and increased oxidative stress-induced cell death compared with vehicle. In the chemotherapy-treated cell line, pharmacological inhibition of CysLT1 or CysLT1 and CYSLTR2 with tool compounds decreased cell death compared with vehicle. In a mouse model of 5-FU-induced kidney damage, each tool compound or the generic LTC4 inhibitor zileuton decreased morbidity and mortality compared with vehicle. Next steps could include testing inhibitors of LTC4, CysLT1 and CYSLTR2 in additional models of chemotherapy-induced toxicity.

Zileuton is marketed to treat asthma...