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CAS No.: 1883545-60-5

CRT0066101 2HCl Catalog No. CSN22547

Synonyms: CRT0066101 2HCl;CRT-0066101;CRT0066101 HCl

CRT0066101 reduces BrdU incorporation, increases apoptosis, blocks neurotensin (NT)-induced PKD1/2 activation, reduces NT-induced PKD-mediated Hsp27 phosphorylation, attenuates PKD1-mediated NF-κB activation, and abrogates expression of NF-κB-dependent-dependent proliferative and pro-survival proteins.

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技术信息

生物活性

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].
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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.4311 mL
- 12.1557 mL
- 24.3115 mL
- 5 mM
- 0.4862 mL
- 2.4311 mL
- 4.8623 mL
- 10 mM
- 0.2431 mL
- 1.2156 mL
- 2.4311 mL

技术信息

CAS号	1883545-60-5	储存条件	粉末 Inert atmosphere,2-8°C 液体 -20°C:3-6 月 -80°C:12月
分子式	C18H24Cl2N6O	运输	蓝冰
分子量	411.33	别名	CRT0066101 2HCl;CRT-0066101;CRT0066101 HCl;CRT0066101 hydrochloride

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