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CRT0066101 2HCl

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Chemical Structure| 1883545-60-5 同义名 : CRT0066101 dihydrochloride
CAS号 : 1883545-60-5
货号 : A226191
分子式 : C18H24Cl2N6O
纯度 : 99%+
分子量 : 411.329
MDL号 : MFCD30182249
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 10 mg/mL(24.31 mM)，配合低频超声，并水浴加热至45℃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

H2O: 50 mg/mL(121.56 mM)，配合低频超声助溶
动物实验配方：
生物活性
靶点

  • PKD

    PKD2, IC50:2 nM

    PKD1, IC50:1 nM
描述 Protein kinase D (PKD, also known as PKCmu) is closely related to the protein kinase C superfamily but is differentially regulated and has a distinct catalytic domain that shares homology with Ca(2+)-dependent protein kinases. PKD is highly expressed in hematopoietic cells and undergoes rapid and sustained activation upon stimulation of immune receptors. PKD is regulated through phosphorylation by protein kinase C (PKC)[1]. CRT0066101 dihydrochloride is a potent and specific PKD inhibitor with IC50 values of 1, 2.5 and 2 nM for PKD1, 2, and 3 respectively. CRT0066101 specifically blocks PKD1/2 activity and does not suppress PKCα/PKCβ/PKCε activity in multiple cancer cell types including A549 (lung) and MiaPaCa-2 (pancreas). CRT0066101 significantly inhibits Panc-1 cell proliferation with an IC50 value of 1 µM. Treatment with CRT0066101 results in a 6-10 fold induction of apoptosis in Panc-1 cells. CRT0066101 significantly reduces cell proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells but has a modest effect in Capan-2 cells. CRT0066101 (5 µM) blocks both the basal and NT-induced pS916-PKD1/2 (activated PKD1/2) in Panc-1 and Panc-28 cells. CRT0066101 reduces PKD-dependent NF-κB activation and NF-κB-dependent gene expressions in Panc-1. Optimal therapeutic concentrations (8 µM) of CRT0066101 are detectable 6 h after oral administration of this drug. CRT0066101 given orally (80 mg/kg/day) for 28 days significantly abrogates PaCa growth in Panc-1 subcutaneous xenograft model. Activated PKD1/2 expression in the treated tumor-explants is significantly inhibited with peak tumor concentration (12 µM) of CRT0066101 achieved within 2 h after oral administration. Further, CRT0066101 given orally (80 mg/kg/day) for 21 days in Panc-1 orthotopic model potently blocks tumor growth in vivo. CRT0066101 significantly reduces Ki-67+ proliferation index, increases TUNEL+ apoptotic cells (p<0.05), and abrogates expression of NF-κB-dependent proteins including cyclin D1, survivin, and cIAP-1[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.43mL

0.49mL

0.24mL

12.16mL

2.43mL

1.22mL

24.31mL

4.86mL

2.43mL
参考文献

[1] Margaret J Stafford,et al. PKD: a new protein kinase C-dependent pathway in platelets. Blood. 2003 Feb 15;101(4):1392-9.

[2]Harikumar KB, et al. A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2010 May;9(5):1136-46.