生物活性
SPHINX31 is a potent inhibitor of serine/arginine-rich protein kinase 1 (SRPK1) with IC50 of 5.9 nM. SPHINX31 inhibits phosphorylation of serine/arginine-rich splicing factor 1 (SRSF1). SPHINX31 treatment results in inhibition of SRSF1 phosphorylation at 300 nM in PC3 prostate cancer cells. Metabolic stability in mouse liver microsomes shows that SPHINX31 had medium clearance with a T1/2 of 95.79 min.
In vivo, SPHINX31 exerts a dose dependent inhibition of choroidal neovascularisation in mouse model. SPHINX31 inhibits blood vessel growth and macrophage infiltration. SPHINX31 treatment prolongs survival of immunocompromised mice transplanted with MLL-rearranged AML cells.
化学数据
| 分子量 | 507.51 |
| 分子式 | C27H24F3N5O2 |
| CAS号 | 1818389-84-2 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO 18 mg/mL |
| 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 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | THP-1 cells |
| 方法 | For synergy studies between SPHINX31 and iBET, THP-1 cells were seeded in 96-well plates at 10,000 cells per well and treated with SPHINX31 (dose range of 0.039–5 μM) and iBET (dose range of 9.8–312.5 nM) in an 8 by 6 matrix. Each treatment was carried out in triplicate. Cells were treated for 72 h, and cell viability was determined using CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay (Promega) in order to calculate the relative cell proliferation. Cell viability for each treatment was normalized against the DMSO control group. A Bliss independence model was employed to evaluate combination effects and calculate the Bliss independence score. All the compounds were dissolved in DMSO. |
| 浓度 | 0.039-5 μM |
| 处理时间 | 72 h |
| 动物实验 |
|---|
| 动物模型 | DBA2J mice |
| 配制 | dissolved in 20%(w/v) 2-hydroxyproply beta-cyclodextrin vehicle |
| 剂量 | 0.8 mg/kg |
| 给药处理 | i.p. |
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 | 1.9704 mL | 9.852 mL | 19.704 mL |
| 5 mM | 0.3941 mL | 1.9704 mL | 3.9408 mL |
| 10 mM | 0.197 mL | 0.9852 mL | 1.9704 mL |
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