Antibodies
Palbociclib (PD0332991) Isethionate
- 貨號 Cat. No.
- S1579
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Palbociclib (PD0332991) IsethionateLicensed and Manufactured by Pfizer
Palbociclib (PD0332991) Isethionate is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 2/3.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Palbociclib (PD0332991) Isethionate is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 2/3. | |||||
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| Targets | CDK4 | CDK6 | ||||
| IC50 | 11 nM | 16 nM [1] | ||||
| 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(Only for 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. |
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Cell Assay: [3]
| Cell lines | Human breast cancer cells MDA-MB-435 |
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| 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 |
| Solubility | Saline, 30 mg/mL |
References
Chemical Information
Download Palbociclib (PD0332991) Isethionate SDF
| Molecular Weight (MW) | 573.66 |
|---|---|
| Formula | C24H29N7O2.C2H6O4S |
| CAS No. | 827022-33-3 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | <1 mg/mL (<1 mM) |
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| Water | 100 mg/mL (174 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | Saline, | 30 mg/mL | |
| * <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. | |||
| Chemical Name | Ethanesulfonic acid, 2-hydroxy-, compd. with 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one (1:1) |
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Customer Reviews (1)
 Click to enlarge | Rating | |
| Source | Helen Sadik from Johhns Hopkins University. Palbociclib (PD0332991) Isethionate purchased from Selleck | |
| Method | MTT | |
| Cell Lines | MCF10A-Ras,MDA-MB-231, SUM159, MCF-7 cells | |
| Concentrations | ||
| Incubation Time | 24 h | |
| Results | Different breast cancer cell lines were seeded in 96 well plates and treated with different concentrations of PD0332991. After 72h, cell viability was assessed by MTT. Data shows that these cancer cell lines had a better response to CDK4/6 inhibition than the less tumorigenic MCF10A-Ras cells. |
Product Citations (6)
Combined targeting of MEK and PI3K/mTOR effector pathways is necessary to effectively inhibit NRAS mutant melanoma in vitro and in vivo. [Posch C , et al. Proc Natl Acad Sci U S A 2013;110(10):4015-20]
Flavopiridol Synergizes with Sorafenib to Induce Cytotoxicity and Potentiate Antitumorigenic Activity in EGFR/HER-2 and Mutant RAS/RAF Breast Cancer Model Systems. [Nagaria TS, et al. Neoplasia 2013;15(8):939-51]
CDK4/6-inhibiting drug substitutes for p21 and p16 in senescence: duration of cell cycle arrest and MTOR activity determine geroconversion. [Leontieva OV, et al. Cell Cycle 2013;12(18):3063-9]
