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Amuvatinib

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Chemical Structure| 850879-09-3 同义名 : MP470;HPK 56
CAS号 : 850879-09-3
货号 : A205668
分子式 : C23H21N5O3S
纯度 : 99%+
分子量 : 447.51
MDL号 : MFCD16038298
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(111.73 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：

5%DMSO+95% Corn oil 4.5 mg/mL

生物活性
靶点

  • PDGFRα

    PDGFRα (V561D), IC50:40 nM

  • c-Kit

    c-Kit (D816H), IC50:10 nM

  • FLT3

    FLT3 (D835Y), IC50:81 nM
描述 c-KIT is a tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. c-KIT is a proto-oncogene. Activating or gain of function mutations in c-KIT have been identified in a variety of tumors[3]. Amuvatinib, also termed MP470, is an inhibitor of various mutant c-KIT kinases. The inhibitory IC50s of MP470 against c-KIT(D816V), c-KIT(D816H), c-KIT(V560G), c-KIT(V654A) were 0.95 μM, 0.01 μM, 0.034 μM and 0.127 μM, respectively. The IC50 for MP470 on OVCAR-3 cells proliferation was 0.9 μM[3]. According to another report, the IC50 for MP470 on prostate cancer LNCaP and PC-3 cells were ~4 μM and 8 μM, respectively, when incubated for 4 days. Flow cytometric analysis revealed that 48h treatment of MP470 to LNCaP cells at the concentration of 10 μM induced 28% of apoptosis[4]. In a HT-29 xenograft model, MP470 was i.p. administrated at the doses of 10 or 20 mg/kg at the schedule of 5 times a week for 2 weeks. Both doses significantly inhibited tumor growth. In an A549 xenograft model, MP470 was orally administrated at the doses of 50, 100, or 200 mg/kg, also 5 times a week for 2 weeks. All three doses exhibited anti-tumor activity[3]. In another LNCaP xenograft model, MP470 was i.p. dosed at 50 mg/kg daily for 24 days. This dose in combination with Erlotinib had a marked effect with tumor growth inhibition of 45-65%, while both drugs were of modest activity as a single agent[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.23mL

0.45mL

0.22mL

11.17mL

2.23mL

1.12mL

22.35mL

4.47mL

2.23mL
参考文献

[1]Qi W, Cooke LS, et al. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142.

[2]Mahadevan D, Cooke L, et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene. 2007 Jun 7;26(27):3909-19.

[3]PHARMACEUTICAL FORMULATIONS COMPRISING SALTS OF A PROTEIN KINASE INHIBITOR AND METHODS OF USING SAME

[4]Qi W, Cooke LS, Stejskal A, Riley C, Croce KD, Saldanha JW, Bearss D, Mahadevan D. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142.