帕布昔利布鹽酸鹽作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetPalbociclib hydrochlorideCat. No.: HY-50767ACAS No.: 827022-32-2分式: CHClNO分量: 483.99作靶點(diǎn): 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)體外實(shí)驗(yàn) DMSO : 5.4 mg/mL (11.16 mM; Need ultrasonic)H2O : 4.9 mg/mL (10.12 mM; Need ultrason

2、ic and warming)SolventMass1 mg 5 mg 10 mgConcentration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；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時(shí)，請?jiān)?6 個(gè)內(nèi)使，-20C 儲存時(shí)，請?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請

3、根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶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 solution此案可獲得 0.54 mg/mL (1.12 mM

4、，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 5.4 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.54 mg/mL (1.12 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 0.54 mg/mL (1.12 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取

5、100 L 5.4 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 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。Palbociclib hydrochloride 有潛于 ER 陽性和

6、HER2陰性乳腺癌的研究。IC & Target Cdk4/cyclin 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 in MDA-MB-435breast carcinoma cells is 66 nM. Pal

7、bociclib is equally effective at reducing Rb phosphorylation at Ser795 in this tumorwith an IC50 of 63 nM, and similar effects on both Ser780 and Ser795 phosphorylation are obtained in the Colo-205colon carcinoma1. The MP-MRT-AN (AN), KP-MRT-RY (RY), G401, and KP-MRT-NS (NS) cell lines are effective

8、lyinhibited by Palbociclib (PD) in 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 cytometry results show that Palbociclib at concentrations betw

9、een 0 to 1.0 M induces G1 arrest in the AN,RY, G401 and 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 BrdU incorporation(indicating G1 arrest) in the AN, RY, G401 an

10、d NS cell lines, but not in the YM cell line. Palbociclib, even at aconcentration of 0.05 M, significantly reduces BrdU incorporation in the AN, RY, and G401 cell lines (p1 log oftumor cell kill at the highest dose tested. At 37.5 mg/kg, the tumor slowly regressed during treatment. Even at dosesas l

11、ow as 12.5 mg/kg, a 13-day growth delay is obtained indicating 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 isapparent at 150 mg/kg and some cell kill is evident at the highest dose1.PRO

12、TOCOLKinase Assay 1 CDK assays are performed in 96-well filter plates. All CDK-cyclin kinase complexes are expressed in insect cellsthrough baculovirus infection and purified. The substrate for the assays is a fragment (amino acids 792-928) of pRbfused to GST (GSTRB-Cterm). The total volume in each

13、well is 0.1 mL containing a final concentration of 20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2, 25 M ATP (for CDK4-cyclin D1, CDK6-cyclin D2, andCDK6-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,

14、1 g of GSTRB-Cterm, and Palbociclib (0.001-0.1M). All components except the -32PATPare added to the wells, and the plate is placed on a plate mixer for 2 min. The reaction is started by adding the -32PATP and the plate is incubated at 25C for 15 min. The reaction is terminated by addition of 0.1 mL

15、of 20%trichloroacetic acid and the plate is kept at 4C for at least 1 hour to allow the substrate to precipitate. The wells arePage 2 of 3 www.MedChemEthen washed 5 times with 0.2 mL of 10% trichloroacetic acid and radioactive incorporation is determined with a plate counter.MCE has not independentl

16、y 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) cell lines areseeded in normal growth medium into 96-well cell plates. After 24 h, the culture medium is replaced with culturem

17、edium containing Palbociclib (0.05 or 1 M) or DMSO. Cells are cultured and treated in triplicate. Cell proliferationis determined 8 days after the treatment by WST-8 assay using a Cell Counting Kit-8.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Anima

18、l Mice (18-22 g) are randomized and then implanted s.c. with tumor fragments (30 mg) into the region of the rightAdministration 1 axilla. Treatment is initiated when tumors reach 100 to 150 mg. PD 0332991 (150 or 75 mg/kg, p.o.) is givenaccording to the schedule and dose indicated in the table and f

19、igure legends by gavage as a solution in sodiumlactate buffer (50 mM, pH 4.0) based on mean group body weight. In all experiments, there are 12 mice in the controlgroup and 8 mice each in the treated groups. Additional details for each experiment are given in the table legends.MCE has not independen

20、tly confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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. 2020 May 7;S1097-2765(20)30269-0.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Fry DW, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD