NSC-663284-DA-3003-1-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENSC 663284Cat. No.: HY-100034CAS No.: 383907-43-5Synonyms: DA-3003-1分式: CHClNO分量: 321.76作靶点: Phosphatase作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 150 mg/

2、mL (466.19 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.1079 mL 15.5395 mL 31.0791 mL5 mM 0.6216 mL 3.1079 mL 6.2158 mL10 mM 0.3108 mL 1.5540 mL 3.1079 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保

3、证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.77 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.77 mM); Clear solution1/3 Master of Small Molec

4、ules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.77 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 NSC 663284是Cdc25 双重 特异性磷酸酶抑制剂， IC50 值为0.21 M。IC50 & Target IC50: 0.21 M (Cdc25 dual specificity phosphatase) 1体外研究 The Cdc25 dual specificity phosphatases have central rol

5、es in coordinating cellular signaling processes andcell proliferation. NSC 663284 exhibits mixed competitive kinetics against Cdc25A, Cdc25B2, and Cdc25Cwith Ki values of 29, 95, and 89 nM, respectively. NSC 663284 blocks cellular Erk dephosphorylation causedby ectopic Cdc25A expression. NSC 663284

6、displays a strong preference for Cdc25B2 as compared withVHR or PTP1B, the relative IC50 values for Cdc25B2 are 20- and 450-fold lower than for VHR or PTP1B,respectively. NSC 663284 blocks cell proliferation and the actions of cellular cdc25a. NSC 663284 has amean IC50 value in the NCI 60 Cell Human

7、 Tumor Panel of 1.5 (0.6 M when cells are treated for 48 h).Most sensitive are human breast cancer MDA-MB-435 and MDA-N cells, which have IC50 values of 0.2 M1.体内研究 NSC 663284 inhibits the growth of subcutaneous human colon HT29 xenografts in SCID mice. After a singlei.v. dose of 5 mg/kg, NSC 663284

8、 is not detectable in plasma or tissues beyond 5 min. Following NSC663284 treatment of tumor-bearing SCID mice, reduces glutathione concentrations in HT29 tumor aredecreased to a greater extent and remained decreased for longer than the reduced glutathioneconcentrations in liver and kidneys 2.PROTOC

9、OLAnimal Mice: C.B.-17 SCID mice bearing HT29 human colon carcinoma xenografts are stratified into the followingAdministration 2 groups of 9-10 animals: Control, vehicle control, positive control (gemcitabine, 50 mg/kg/dose i.v.), NSC663284 at the following doses: 2, 3 or 5 mg/kg/dose i.v. The mice

10、are dosed every 4 days for 6 doses, andbody weights and tumor volumes are recorded twice weekly. Tumors are measured with calipers, and tumorvolumes are calculated. Mice are followed for 3 weeks following the completion of the dosing to monitortumor regrowth. In a second study, C.B.-17 SCID mice bea

11、ring MDA-MB-435 human breast cancerxenografts are stratified to the same treatment groups, except that paclitaxel at 20 mg/kg i.v. every 7 days isused as the positive control 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lazo JS, et al.

12、 Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25.J Med Chem. 2001 Nov 22;44(24):4042-9.2. Guo J, et al. Pharmacology and antitumor activity of a quinolinedione Cdc25 phosphatase inhibitor DA3003-1 (NSC 663284). Anticancer2/3 Master of Small Molecules 您边的抑制剂师www.MedChemERes. 2007 Sep-Oct;27(5A):3067-73.McePdfHeightCautio