CRT0066101-dihydrochloride - PKD 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECRT0066101 dihydrochlorideCat. No.: HY-15698ACAS No.: 1883545-60-5分式: CHClNO分量: 374.87作靶點: PKD作通路: Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 25 mg/mL (66.69 mM)* means solubl

2、e, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.6676 mL 13.3380 mL 26.6759 mL5 mM 0.5335 mL 2.6676 mL 5.3352 mL10 mM 0.2668 mL 1.3338 mL 2.6676 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 CRT0066101 dihydrochloride是有效，選擇性的 PKD 抑制劑，對PKD1，2和3的IC5

3、0值分別為1，2.5和2 nM。IC50 & Target PKD1 PKD3 PKD21 nM (IC50) 2 nM (IC50) 2.5 nM (IC50)體外研究CRT0066101 specifically blocks PKD1/2 activity and does not suppress PKC/PKC/PKC activity in multiple1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEcancer cell types including A549 (lung) and MiaPaCa-2 (pancreas).

4、 CRT0066101 significantly inhibits Panc-1cell proliferation with an IC50 value of 1 M. Treatment with CRT0066101 results in a 6-10 fold induction ofapoptosis in Panc-1 cells. CRT0066101 significantly reduces cell proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells but has a modest effect i

5、n Capan-2 cells. CRT0066101 (5 M) blocks both the basal andNT-induced pS916-PKD1/2 (activated PKD1/2) in Panc-1 and Panc-28 cells. CRT0066101 reduces PKD-dependent NF-B activation and NF-B-dependent gene expressions in Panc-1 1.體內(nèi)研究 Optimal therapeutic concentrations (8 M) of CRT0066101 are detectab

6、le 6 h after oral administration of thisdrug. CRT0066101 given orally (80 mg/kg/day) for 28 days significantly abrogates PaCa growth in Panc-1subcutaneous xenograft model. Activated PKD1/2 expression in the treated tumor-explants is significantlyinhibited with peak tumor concentration (12 M) of CRT0

7、066101 achieved within 2 h after oral administration.Further, CRT0066101 given orally (80 mg/kg/day) for 21 days in Panc-1 orthotopic model potently blockstumor growth in vivo. CRT0066101 significantly reduces Ki-67+ proliferation index, increases TUNEL+apoptotic cells (p 1.PROTOCOLAnimal Mice: Nine

8、teen days after implantation of Panc-1 cells, tumor areas are, on average 0.3 cm2 and areAdministration 1 randomized into the following groups (n=8 mice per group): (a) vehicle (control) 5% dextrose administered byoral gavage once daily and (b) 80 mg/kg CRT0066101 dissolved in 5% dextrose administer

9、ed by oral gavageonce daily. Tumors are measured in 2 dimensions every 2 to 3 days by calipers and area is calculated bymultiplying length by width. Therapy is given until tumors reached their designated size limits (1.44 cm2) oruntil day 24 in CRT0066101 treated group. Final tumor areas are compare

10、d among groups using a Studentst test and Fishers exact test with p 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Harikumar KB, et al. A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo. MolCancer Ther. 2010 May;9(5):1136-46.McePdfHeightCaution: Product has not been fully va