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受注：045-509-1970 |
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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C24H29N7O2.HCl |
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| 分子量 | 483.99 | CAS No. | 827022-32-2 | |
| Solubility (25°C)* | 体外 | Water | 34 mg/mL warmed with 50ºC water bath (70.24 mM) | |
| DMSO | 4 mg/mL warmed with 50ºC water bath (8.26 mM) | |||
| Ethanol | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | パルボシクリブ塩酸塩 (Palbociclib (PD-0332991) HCl) は選択性の高い CDK4/6 阻害剤であり、cell-free assay における IC50 はそれぞれ 11 nM/ 16 nM です。CDK1/2/5, EGFR, FGFR, PDGFR, InsR その他のターゲットに対しては活性を有しません。臨床第3相試験中 |
|---|---|
| in vitro | PD 0332991 has little effect on other protein kinases including EGFR, FGFR, PGFR, IR. PD 0332991 is a non-ATP competitive inhibitor of Cdk4. PD 0332991 inhibits MDA-MB-435 breast carcinoma cells with IC50 of 66 nM, which is due to reduced Rb phosphorylation at Ser780. PD 0332991 inhibits thymidine incorporation into the DNA of Rb-positive human breast, colon, and lung carcinomas as well as human leukemias, with IC50 values ranging from 0.04-0.17 μM. PD 0332991 shows no activity in Rb-negative cells. PD 0332991 causes an accumulation of cells in G1 in MDA-MB-453 breast and Colo-205 carcinoma cells. [1] PD 0332991 also shows activity in 5T33MM myeloma cells (immunocompetent model) and sensitizes the cells to killing by bortezomib. [2] PD 0332991 inhibits luminal ER-positive as well as HER2-amplified breast cancer cell lines including MDA-MB-175, ZR-75-30, CAMA-1, MDA-MB-134, HCC-202 and UACC-893. PD 0332991 enhances the activity of tamoxifen and trastuzumab in these cell lines. PD 0332991 enhances the sensitivity of tamoxifen in the MCF7 tamoxifen-resistant cells. [3] A recent study shows that PD 0332991 could suppress malignant rhabdoid tumor (MRT) cell lines including MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS and the sensitivity of the MRT cell lines to PD 0332991 is inversely correlated with expression of p16. [4] |
| in vivo | PD 0332991 indicates complete tumor stasis in a MDA-MB-435 xenograft at 150 mg/kg. PD 0332991 also shows broad-spectrum antitumor activity in multiple human tumor xenografts by eliminating phospho-Rb and the proliferative marker Ki-67 from tumor tissue and down-regulation of genes under the transcriptional control of E2F. [1] |
| 特徴 | Non-cytotoxic, and halts cancer cell growth & could be used in glioblastoma that has relapsed after temozolomide treatment (a chemotherapeutic used to treat many cancers). |
プロトコル(参考用のみ)
| キナーゼアッセイ | Cdk Assays | |
|---|---|---|
| A stock solution of PD0332991 is prepared in DMSO. CDK assays 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 volume in each 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 μM ATP (for CDK4-cyclin D1, CDK6-cyclin D2, and CDK6-cyclin D3) or 12 μM ATP (for CDK2-cyclin E, CDK2-cyclin A, and CDC2-cyclin B) containing 0.25 μCi of [γ-32P]ATP, 20 ng of enzyme, 1 μg of GST·RB-Cterm, and PD 0332991 (0.001-0.1μM). All components except the [γ-32P]ATP are added to the wells, and the plate is placed on a plate mixer for 2 min. The reaction is started by adding the [γ-32P]ATP and the plate is incubated at 25 °C for 15 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid and the plate is kept at 4 °C for at least 1 hour to allow the substrate to precipitate. The wells are then washed 5 times with 0.2 mL of 10% trichloroacetic acid and radioactive incorporation is determined with a β plate counter. | ||
| 細胞アッセイ | 細胞株 | Tumor cell lines including MDA-MB-435, ZR-75-1, T-47D, MCF-7, H1299, Colo-205, MDA-MB-468, H2009, CRRF-CEM and K562 |
| 濃度 | 0.01-1 μM | |
| 反応時間 | 24 hours | |
| 実験の流れ | Cells are seeded at 2 × 104 per well in a 96-well plate and incubated overnight. PD 0332991 (0.01-1 μM) is added to the wells and incubated at 37 °C for another 24 hours. [14C]Thymidine (0.1 μCi) is added to each well and incorporation of the radiolabel is allowed to proceed for 72 hours. Incorporated radioactivity is determined with a β plate counter. |
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| 動物実験 | 動物モデル | Advanced stage human tumor xenografts including Colo-205, MDA-MB-435 breast, SF-295 glioblastoma, ZR-75-1 breast, PC-3 prostate, H125 lung, SW-620 colon, H23 lung and MDA-MB-468 breast (Rb negative) are established in severe combined immunodeficient mice. |
| 投薬量 | 0-150 mg/kg | |
| 投与方法 | Given by gavage | |
参考
カスタマーフィードバック
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Data from [Pharmacogenomics J, 2013, 13(1), 94-104]
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Data from [Clin Transl Oncol, 2012, 14(3), 197-206 ]
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Data from [Clin Cancer Res, 2011, 17(13), 4513-22]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| An intermediate Rb-E2F activity state safeguards proliferation commitment [ Nature, 2024, 631(8020):424-431] | PubMed: 38926571 |
| Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers [ Science, 2024, 384(6700):eadk0775] | PubMed: 38843331 |
| Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment [ Cancer Cell, 2024, S1535-6108(24)00037-0] | PubMed: 38402610 |
| Cyclin-dependent kinase 4 drives cystic kidney disease in the absence of mTORC1 signaling activity [ Kidney Int, 2024, S0085-2538(24)00627-6] | PubMed: 39218392 |
| Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry [ Nat Commun, 2024, 15(1):3220] | PubMed: 38622115 |
| A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis [ Nat Commun, 2024, 15(1):775] | PubMed: 38278798 |
| Uncoupling of mTORC1 from E2F activity maintains DNA damage and senescence [ Nat Commun, 2024, 15(1):9181] | PubMed: 39448567 |
| Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] | PubMed: 38453961 |
| Type II topoisomerases shape multi-scale 3D chromatin folding in regions of positive supercoils [ Mol Cell, 2024, S1097-2765(24)00830-X] | PubMed: 39486417 |
| A p38 MAPK-ROS axis fuels proliferation stress and DNA damage during CRISPR-Cas9 gene editing in hematopoietic stem and progenitor cells [ Cell Rep Med, 2024, 5(11):101823] | PubMed: 39536752 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。