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SP-141

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Chemical Structure| 1253491-42-7 同义名 : AGN-PC-0D106I
CAS号 : 1253491-42-7
货号 : A909933
分子式 : C22H16N2O
纯度 : 99%+
分子量 : 324.375
MDL号 : MFCD29059920
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(369.94 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Mouse Double Minute 2 (MDM2) is an oncogene that contributes to the progression and metastasis of breast cancer and is associated with poor prognosis in breast cancer patients. SP-141 is a specific MDM2 inhibitor that directly binds to the MDM2 protein with a Ki value of 28±6nM in the FP-based assay and a KD value of 43 nM in the Biacore assay. SP-141 inhibited breast cancer cell growth (MCF-7/p53 wild-type, MCF-7/p53 knockdown, MDA-MB-468/p53 mutant, MDA-MB-231/p53 mutant, and MDA-MB-435/p53 mutant) with IC50 values ranging from 0.39 – 0.91μM. In MCF-7/p53 wild-type, MCF-7/p53 knockdown, and MDA-MB-468/p53 mutant cells, SP-141 at a concentration of 1μM increased apoptosis rate 14-, 7-, and 11-fold, respectively, relative to control cells. SP-141 also significantly induced cell cycle arrest in the G2 phase at a concentration of 0.5μM. The expression of cleaved PARP and Bax was increased, while that of Bcl-2 and Cyclin E was decreased in SP-141-treated breast cancer cells in a p53-independent manner. Intraperitoneal injection of SP-141 at a dose of 40mg/kg/day for 42 and 30 days inhibited tumor growth in nude mice bearing MCF-7 (by ~82%) and MDA-MB-468 (by ~80%) xenograft tumors, respectively.[1]
作用机制 SP-141 is a specific MDM2 inhibitor that shows a strong binding capacity for the MDM2 protein. The binding site of SP-141 is in the hydrophobic groove of MDM2. SP-141 destabilizes the MDM2 protein in vitro by promoting its ubiquitination.[1]
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01421511 Skin and Subcutaneous Tissue B... 展开 >>acterial Infections 收起 << Phase 3 Completed - -
NCT01421511 - Completed - -
NCT00824265 Leukaemia, Lymphocytic, Chroni... 展开 >>c 收起 << Phase 3 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.08mL

0.62mL

0.31mL

15.41mL

3.08mL

1.54mL

30.83mL

6.17mL

3.08mL
参考文献

[1]Wang W, Qin JJ, Voruganti S, Srivenugopal KS, Nag S, Patil S, Sharma H, Wang MH, Wang H, Buolamwini JK, Zhang R. The pyrido[b]indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models. Nat Commun. 2014 Oct 1;5:5086. doi: 10.1038/ncomms6086