Palbociclib-PD-0332991-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPalbociclibCat. No.: HY-50767CAS No.: 571190-30-2Synonyms: PD 0332991分式: CHNO分量: 447.53作靶点: CDK作通路: Cell Cycle/DNA Damage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 : 0.2 mg/mL (0.45 mM;

2、Need ultrasonic and warming)H2O : 10 M). The flow cytometryresults show that Palbociclib at concentrations between 0 to 1.0 M induces G1 arrest in the AN, RY, G401and NS cell lines in a concentration-dependent manner, but has no effect on YM cells. The BrdUincorporation results are consistent with t

3、he WST-8 and flow cytometry results: PD reduces BrdUincorporation (indicating G1 arrest) in the AN, RY, G401 and NS cell lines, but not in the YM cell line.Palbociclib, even at a concentration of 0.05 M, significantly reduces BrdU incorporation in the AN, RY, andG401 cell lines (p 2.体内研究 Palbociclib

4、 (PD 0332991) exhibits significant antitumor efficacy against multiple human tumor xenograftmodels. In mice bearing Colo-205 colon carcinoma xenografts (p16 deleted), daily p.o. dosing for 14 dayswith Palbociclib (150 or 75 mg/kg) produces rapid tumor regressions and a corresponding tumor growthdela

5、y of 50 days with 1 log of tumor cell kill at the highest dose tested. At 37.5 mg/kg, the tumor slowlyregressed during treatment. Even at doses as low as 12.5 mg/kg, a 13-day growth delay is obtainedindicating a 90% inhibition of tumor growth rate. Likewise, robust antitumor activity is seen in the

6、MDA-MB-435 breast carcinoma (p16 deleted) where complete tumor stasis is apparent at 150 mg/kg and some cell killis evident at the highest dose 1.PROTOCOLKinase Assay 1 CDK assays are performed in 96-well filter plates. All CDK-cyclin kinase complexes are expressed in insectcells through baculovirus

7、 infection and purified. The substrate for the assays is a fragment (amino acids 792-928) of pRb fused to GST (GSTRB-Cterm). The total volume in each well is 0.1 mL containing a finalconcentration of 20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2, 25 M ATP (forCDK4-cyclin D1, C

8、DK6-cyclin D2, and CDK6-cyclin D3) or 12 M ATP (for CDK2-cyclin E, CDK2-cyclin A,and CDC2-cyclin B) containing 0.25 Ci of -32PATP, 20 ng of enzyme, 1 g of GSTRB-Cterm, andPalbociclib (0.001-0.1M). All components except the -32PATP are added to the wells, and the plate isplaced on a plate mixer for 2

9、 min. The reaction is started by adding the -32PATP and the plate is incubatedat 25C for 15 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid and the plateis kept at 4C for at least 1 hour to allow the substrate to precipitate. The wells are then washed 5 times with0.

10、2 mL of 10% trichloroacetic acid and radioactive incorporation is determined with a plate counter.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 MRT cell lines, G401, MP-MRT-AN (AN), KP-MRT-RY (RY), KP-MRT-NS (NS), and KP-MRT-YM (YM) celll

11、ines are seeded in normal growth medium into 96-well cell plates. After 24 h, the culture medium is replacedwith culture medium containing Palbociclib (0.05 or 1 M) or DMSO. Cells are cultured and treated intriplicate. Cell proliferation is determined 8 days after the treatment by WST-8 assay using

12、a Cell CountingKit-8.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAnimal Mice (18-22 g) are randomized and then implanted s.c. with tumor fragments (30 mg) into the region of theAdministration 1 right

13、axilla. Treatment is initiated when tumors reach 100 to 150 mg. PD 0332991 (150 or 75 mg/kg, p.o.) isgiven according to the schedule and dose indicated in the table and figure legends by gavage as a solution insodium lactate buffer (50 mM, pH 4.0) based on mean group body weight. In all experiments,

14、 there are 12mice in the control group and 8 mice each in the treated groups. Additional details for each experiment aregiven in the table legends.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Nature. 2017 Aug 24;548(7668):471-475. Nature.

15、 2017 Jun 15;546(7658):426-430. Cancer Cell. 2017 Apr 10;31(4):576-590.e8. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Mol Cell. 2017 Oct 19;68(2):336-349.e6.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Fry DW, et al. Specific inhibition of cyclin-dependent kinase 4/

16、6 by PD 0332991 and associated antitumor activity in human tumorxenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.2. Katsumi Y, et al. Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression. BiochemBiophys Res Commun, 2011, 413(1), 62-68.3. Goel S, et al. CDK4/6 inhibition triggers anti-tumour immun