Lonafarnib (Sch66336) showcases exceptional oral bioavailability and pharmacokinetic profiles across mouse, rat, and monkey models. In studies using nude mice, Lonafarnib has shown significant efficacy when administered orally against a variety of human cancer xenografts, including those from the colon, lung, pancreas, prostate, and bladder^[1].

Administered alone at a dosage of 80 mg/kg orally once a day, Lonafarnib shows a modest capacity to suppress the growth of orthotopic U87 tumors, with a therapeutic/control ratio (T/C) of 0.67, when compared to animals treated with the control vehicle. The regimen of XRT/Tem, involving 2.5Gy of radiation therapy per day for two days coupled with Temozolomide at 5 mg/kg given orally 90 minutes before radiation, is engineered to achieve a moderate level of tumor growth inhibition in vivo, demonstrating a T/C ratio of 0.42. A combined treatment involving Lonafarnib, given at 80 mg/kg orally once daily, radiation therapy at 2.5Gy per day for two days, and Temozolomide at 5 mg/kg orally 90 minutes before radiation, results in the most significant reduction of tumor growth (T/C of 0.02). This combination is substantially more effective than just XRT/Tem (p<0.04), with a majority of the subjects showing a reduction in tumor volume after two weeks, a result that remains after four weeks (p<0.05)^[2].

Lonafarnib (Sch66336) effectively disrupts Ha-Ras processing in intact cells and inhibits the abnormal growth characteristics of fibroblasts and human cancer cell lines that carry active Ki-Ras proteins^[1].

Groups treated with Lonafarnib (10 μM) exhibited a marked increase in the levels of unfarnesylated H-Ras (116-137%) when compared to those receiving the control treatment^[2].