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Palbociclib(PD0332991)Isethionate
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Palbociclib(PD0332991)Isethionate图片
CAS NO:827022-33-3
规格:≥98%
包装与价格:
包装价格(元)
50mg电议
100mg电议
250mg电议
500mg电议
1g电议
2g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)573.66
FormulaC24H29N7O2.C2H6O4S
CAS No.827022-33-3 (isethionate salt);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: <1 mg/mL
Water: 50 mg/mL (87.2 mM)
Ethanol:<1 mg/mL
Solubility (In vivo)Saline: 30 mg/mL
SynonymsPD0332991 isethionate salt, PD-0332991; PD 0332991; Palbociclib isethionate salt, Trade name: Ibrance
实验参考方法
In Vitro

In vitro activity: PD 0332991 exhibits absolute selectivity for CDK4/6 with little or no activity against other CDKs. PD 0332991 is effective at reducing Rb phosphorylation at Ser780 and Ser795 in MDA-MB-435 breast carcinoma cells with IC50 of 66 nM and 63 nM, respectively. PD 0332991 is a potent inhibitor of cell growth and suppresses DNA replication by preventing cells from entering S phase. PD 0332991 inhibits thymidine incorporation into the DNA of Rb-positive human breast (such as MDA-MB-435, MCF-7), colon (H1299), and lung carcinomas (Colo-205) as well as human leukemias (CRRF-CEM and K562), with IC50 values ranging from 0.04-0.17 μM. PD 0332991 significant increases the percentage of MDA-MB-453 in G1 period. PD 0332991 inhibits phosphorylation of Rb in cycling CD138+ primary bone marrow myeloma cells, nontransformed primary B cells, MM1.S and CAG HMCLs cells line with IC50 of<0.1 μM, 0.05 μM, and 60-70 nM, respectively. PD 0332991 treatment also induces G1 arrest of CD138+ primary bone marrow myeloma and nontransformed primary B cells. PD 0332991 induces G1 arrest in MM1.S with IC50 of ~0.05 μM. PD 0332991 preferentially inhibits proliferation of luminal estrogen receptor-positive (including HER2-positive) human breast cancer cell lines. PD 0332991 increases gene expression of pRb and cyclin D1 and decreases gene expression of CDKN2A (p16) in most sensitive lines. PD 0332991 enhances sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade.


Kinase Assay: CDK assays for IC50 determinations and kinetic evaluation are performed in 96-well filter plates. All CDK-cyclin kinase complexes are expressed in insect cells through baculovirus infection and purified. The substrate for the assays is a fragment (amino acids 792–928) of pRb fused to GST (GSToRB-Cterm). The total reaction volume 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 μM ATP (for CDK4-cyclin D1, CDK6-cyclin D2, and CDK6-cyclin D3) containing 0.25 μCi of [γ-32P]ATP, 20 ng of enzyme, 1 μg of GSToRB-Cterm, and appropriate dilutions of inhibitor. All components except the [γ-32P]ATP are added to the wells, and placed on a plate mixer for 2 min. The reaction is started by adding the [γ-32P]ATP, and incubated at 25℃ for 15 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid, and the plate is kept at 4 ℃ for at least 1 hr to allow the substrate to precipitate. The wells are then washed five times with 0.2 mL of 10% trichloroacetic acid, and radioactive incorporation is determined with a β plate counter.


Cell Assay: Cells (Human breast cancer cells MDA-MB-435) are seeded in duplicate at 5,000 to 10,000 cells per well in 24-well plates. The day after plating, different concentrations of PD 0332991 are added. Control wells without drug are also seeded. At the end of incubation, cells are trypsinizated and placed in Isotone solution and counted immediately using a Coulter Z2 particle counter.

In VivoPD 0332991(150 mg/kg) produces rapid Colo-205 colon carcinoma xenografts regressions and a corresponding tumor growth delay. PD 0332991 (150 mg/kg) induces complete tumor stasis and cell kill in MDA-MB-435 breast carcinoma. PD 0332991 (150 mg/kg) also induces significant tumor regression in mice bearing the SF-295 glioblastoma xenografts, and in ZR-75-1 breast and PC-3 prostate tumor models (complete suppression of tumor growth). PD 0332991 (150 mg/kg) suppresses Rb Ser780 phosphorylation in MDA-MB-435 breast carcinoma over the full 24-hour period. PD 0332991 (150 mg/kg) down-regulates expression of four E2F-regulated genes CDC2, CCNE2, TK1, and TOP2A in Colo-205 carcinoma xenografts. PD 0332991 also rapidly inhibits myeloma tumor growth.
Animal modelHuman colon carcinoma xenografts Colo-205
Formulation & DosageDissolved in solution in sodium lactate buffer (50 mM, pH 4.0); ~150 mg/kg; i.p. injection
References

Mol Cancer Ther. 2004 Nov;3(11):1427-38; Cancer Res. 2006 Aug 1;66(15):7661-7; Breast Cancer Res. 2009;11(5):R77. doi: 10.1186/bcr2419.