生物活性
CX-6258 inhibited Flt-3 and Pim-3 (IC50=0.134 and 0.016 uM). At 0.5 uM of CX-6258, only Pim-1, Pim-2, Pim-3, and Flt-3 of the 107 kinases tested were inhibited by more than 80%, showing excellent selectivity. CX-6258 was also shown to be a reversible inhibitor of Pim-1 (Ki=0.005 uM). CX-6258 showed robust antiproliferative potencies against all cell lines tested derived from human solid tumors and hematological malignancies. In mechanistic cellular assays with MV-4-11 human AML cells, (13) caused dose-dependent inhibition of the phosphorylation of 2 pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively.Pim-1 inhibition using the small molecule inhibitor CX-6258 (12 mM, 3 h) diminishes endogenous NKX3.1 steady state levels in 22RV1 and LNCaP cells. CX-6258 treatment (12 mM, 3 h) treatment diminished steady-state levels of ectopic NKX3.1 in PC3 cells. CX-6258 treatment resulted in a significant reduction in NKX3.1 half-life. While ectopically expressed NKX3.1 in control cells had a half-life of _90 min, Pim-1 inhibition reduced the half-life to _52 min.
化学数据
| 分子量 | 516.42 |
| 分子式 | C26H27Cl2N3O4 |
| CAS号 | 1353858-99-7 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9364 mL | 9.682 mL | 19.3641 mL |
| 5 mM | 0.3873 mL | 1.9364 mL | 3.8728 mL |
| 10 mM | 0.1936 mL | 0.9682 mL | 1.9364 mL |
