Lonafarnib

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 proteins¹. 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 treatment².

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 proteins¹.

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 treatment².

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 bladder¹.

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) 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 bladder¹.

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.

溶解方案(细胞实验)

DMSO 中的溶解度 : 25 mg/mL (39.13 mM; 超声助溶 (<60°C); 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (3.91 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% (20% SBE-β-CD in Saline)Solubility: ≥ 2.5 mg/mL (3.91 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。"

"方案 三": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (3.91 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"