Palbociclib-hydrochloride-PD-0332991-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPalbociclib hydrochlorideCat. No.: HY-50767ACAS No.: 827022-32-2Synonyms: PD 0332991 hydrochloride分式: CHClNO分量: 483.99作靶點: CDK作通路: Cell Cycle/DNA Damage儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體

2、外實驗 DMSO : 5.4 mg/mL (11.16 mM; Need ultrasonic)H2O : 4.9 mg/mL (10.12 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0662 mL 10.3308 mL 20.6616 mL5 mM 0.4132 mL 2.0662 mL 4.1323 mL10 mM 0.2066 mL 1.0331 mL 2.0662 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。體內(nèi)

3、實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.54 mg/mL (1.12 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.54 mg/mL

4、 (1.12 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： Lactic acid buffer (50 mM, pH 4.0)Solubility: 33.33 mg/mL (68.87 mM); Clear solution; Need ultrasonicBIOLOGICAL ACTIVITY物活性 Palbociclib hydrochloride選擇性的 CDK4/6 抑制劑，IC50 分別為11 nM 和 16 nM。IC50 & Target Cdk4/cycli

5、n D3 Cdk4/cyclin D1 Cdk6/cyclin D2 DYRK1A9 nM (IC50) 11 nM (IC50) 16 nM (IC50) 2000 nM (IC50)MAPK8000 nM (IC50)體外研究 The IC50 of Palbociclib (PD 0332991) for reduction of retinoblastoma (Rb) phosphorylation at Ser780 inMDA-MB-435 breast carcinoma cells is 66 nM. Palbociclib is equally effective at re

6、ducing Rb phosphorylationat Ser795 in this tumor with an IC50 of 63 nM, and similar effects on both Ser780 and Ser795phosphorylation are obtained in the Colo-205 colon carcinoma 1. The MP-MRT-AN (AN), KP-MRT-RY (RY),G401, and KP-MRT-NS (NS) cell lines are effectively inhibited by Palbociclib (PD) in

7、 a concentration-dependent manner in a WST-8 assay. The IC50s are 0.01 M, 0.01 M, 0.06 M, and 0.6 M, respectively.In contrast, the KP-MRT-YM (YM) cell line is resistant to Palbociclib (IC5010 M). The flow cytometryresults show that Palbociclib at concentrations between 0 to 1.0 M induces G1 arrest i

8、n 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 the 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

9、 cell line.Palbociclib, even at a concentration of 0.05 M, significantly reduces BrdU incorporation in the AN, RY, andG401 cell lines (p 2.體內(nèi)研究 Palbociclib (PD 0332991) exhibits significant antitumor efficacy against multiple human tumor xenograftmodels. In mice bearing Colo-205 colon carcinoma xeno

10、grafts (p16 deleted), daily p.o. dosing for 14 dayswith Palbociclib (150 or 75 mg/kg) produces rapid tumor regressions and a corresponding tumor growthdelay 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 a

11、s 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 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

12、.PROTOCOLKinase Assay 1 CDK assays are performed in 96-well filter plates. All CDK-cyclin kinase complexes are expressed in insectcells through baculovirus 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

13、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 (for2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemECDK4-cyclin D1, CDK6-cyclin D2, and CDK6-cyclin D3) or 12 M ATP (for CDK2-cyclin E, CDK2-cyclin A,and CDC2-cyclin

14、 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 min. The reaction is started by adding the -32PATP and the plate is incubatedat 25C for 15 min.

15、 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 with0.2 mL of 10% trichloroacetic acid and radioactive incorporation is determined with a plate counte

16、r.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) celllines are seeded in normal growth medium into 96-well cell plates. After 24 h, the culture medium

17、 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 a Cell CountingKit-8.MCE has not independently confirmed the accuracy of these methods. They are

18、 for reference only.Animal Mice (18-22 g) are randomized and then implanted s.c. with tumor fragments (30 mg) into the region of theAdministration 1 right 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 ind

19、icated 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, there are 12mice in the control group and 8 mice each in the treated groups. Additional details for each experiment aregiven in the table legend

20、s.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Nature. 2017 Aug 24;548(7668):471-475. Nature. 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 4/6 by PD 0332991 and associated a