Palbociclib Isethionate

Catalog No.S1579 Batch:S157905

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Technical Data

Formula

C24H29N7O2.C2H6O4S
Molecular Weight 573.66 CAS No. 827022-33-3
Solubility (25°C)* In vitro DMSO 38.6 mg/mL (67.28 mM)
Water 10 mg/mL (17.43 mM)
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Palbociclib Isethionate is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM in cell-free assays. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 3.
Targets
CDK4/CyclinD3 [1]
(Cell-free assay)		 CDK4/CyclinD1 [1]
(Cell-free assay)		 CDK6/CyclinD2 [1]
(Cell-free assay)
9 nM 11 nM 15 nM
In vitro 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. [1] 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. [2] 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. [3]
In vivo PD 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. [1] PD 0332991 also rapidly inhibits myeloma tumor growth. [2]
Features The 1st specific inhibitor for CDK4/6 to show promise in multiple cancers.

Protocol (from reference)

Kinase Assay:[4]
  • CDK activity assays

    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 (GST•RB-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 GST•RB-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:[3]
  • Cell lines

    Human breast cancer cells MDA-MB-435

  • Concentrations

    2 μM

  • Incubation Time

    6 days

  • Method

    Cells 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.
Animal Study:[1]
  • Animal Models

    Human colon carcinoma xenografts Colo-205

  • Dosages

    150 mg/kg

  • Administration

    o.p. injection every day

Customer Product Validation

Data from [Data independently produced by Biochem J, 2014, 459(3), 513-24]

Data from [Neoplasia, 2013, 15(8), 939-51]

Data from [Data independently produced by Pharmacogenomics J, 2013, 13(1), 94-104]

Data from [Data independently produced by Cell Cycle, 2013, 12(18), 3063-9]

Selleck's Palbociclib Isethionate has been cited by 285 publications

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution [ Cell Mol Life Sci, 2024, 81(1):29] PubMed: 38212474
p21 Prevents the Exhaustion of Cluster of Differentiation 4-Positive T Cells Within the Antitumor Immune Response Against Colorectal Cancer [ Gastroenterology, 2023, S0016-5085(23)05008-4] PubMed: 37734420
Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets [ Nat Commun, 2023, 10.1038/s41467-023-39059-3] PubMed: 37328469
Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets [ Nat Commun, 2023, 14(1):3469] PubMed: 37328469
CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2- Metastatic Breast Cancer [ Clin Cancer Res, 2023, 29(8):1557-1568] PubMed: 36749874
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction" [ J Exp Clin Cancer Res, 2023, 42(1):8] PubMed: 36604765
Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition [ Cancer Res, 2023, 83(2):316-331] PubMed: 36409827
The DNA damage response pathway regulates the expression of the immune checkpoint CD47 [ Commun Biol, 2023, 6(1):245] PubMed: 36882648
DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway [ Commun Biol, 2023, 6(1):1041] PubMed: 37833461

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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