Polmacoxib (CG100649) is a pioneering orally active nonsteroidal anti-inflammatory drug (NSAID) with the unique capability of dual inhibition, targeting COX-2 with an IC50 approximately 0.1 μg/ml and carbonic anhydrase[1]. This first-in-class agent shows promise in inhibiting the growth of colorectal adenomas and tumors in mouse models[2].
体内研究
Polmacoxib efficacy extends to tumor volume and weight reduction in subcutaneous xenograft mouse models using athymic nude mice, where Polmacoxib at doses between 7-15 mg/kg daily from day 27 post-injection to day 111, diminishes tumor volume and weight by 58% and 48%, respectively. This is in comparison to Celecoxib, which shows a 48% and 36% reduction under similar conditions[2].
Additionally, Polmacoxib's effects in orthotopic xenograft mouse models using athymic nu/nu mice, where treatment began on day 14 and continued for eight weeks, revealed a significant reduction in CRC growth. Tumor weight decreased by 70% with a 7 mg/kg dosage and by 83% with a 15 mg/kg dosage, compared to a 70% reduction achieved with a significantly higher dose of 500 mg/kg of Celecoxib[2].
体外研究
In vitro, Polmacoxib effectively curtails COX-2 activity and PGE2 production in human colon cancer cells, HCA-7 and HT-29, at lower doses than Celecoxib when tested over 24 hours with concentrations up to 1 μg/ml. Moreover, when administered orally at a dose of 7 mg/kg daily for eight weeks, it significantly hinders intestinal polyp development in ApcMin/+ mice, demonstrating its preventive potential in colorectal cancer (CRC)[2].
搜索
