Palbociclib (PD-0332991) Hydrochloride

製品コードS1116 バッチS111614

印刷

化学情報

Chemical Structure 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
分子量 483.99 CAS No. 827022-32-2
Solubility (25°C)* 体外 Water (warmed with 50ºC water bath) 50 mg/mL (103.3 mM)
DMSO (warmed with 50ºC water bath) 13 mg/mL (26.86 mM)
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 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.

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.
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

  • https://pubmed.ncbi.nlm.nih.gov/15542782/
  • https://pubmed.ncbi.nlm.nih.gov/18632601/
  • https://pubmed.ncbi.nlm.nih.gov/19874578/
  • https://pubmed.ncbi.nlm.nih.gov/21871868/

カスタマーフィードバック

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

Data from [Clin Transl Oncol, 2012, 14(3), 197-206 ]

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：

Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry [ Nature, 2025, 10.1038/s41586-025-09328-w] PubMed: 40739344
Requirement for Cyclin D1 Underlies Cell Autonomous HIF2-Dependence in Kidney Cancer [ Cancer Discov, 2025, 10.1158/2159-8290.CD-24-1378] PubMed: 40178040
E2F activity determines mitosis versus whole-genome duplication in G2-arrested cells [ Nat Commun, 2025, 16(1):6677] PubMed: 40691182
Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity and gradual electrochemical maturation [ Neuron, 2025, S0896-6273(25)00468-4] PubMed: 40651475
A redox switch in p21-CDK feedback during G2 phase controls the proliferation-cell cycle exit decision [ Mol Cell, 2025, 85(17):3241-3255.e11] PubMed: 40858111
Nanoscale analysis of human G1 and metaphase chromatin in situ [ EMBO J, 2025, 44(9):2658-2694] PubMed: 40097852
MRN-CtIP, EXO1, and DNA2-WRN/BLM act bidirectionally to process DNA gaps in PARPi-treated cells without strand cleavage [ Genes Dev, 2025, 39(9-10):582-602] PubMed: 40127955
Lineage-specific CDK activity dynamics characterize early mammalian development [ Cell Rep, 2025, 44(4):115558] PubMed: 40220290
FXR shapes an immunosuppressive microenvironment in PD-L1lo/- non-small cell lung cancer by upregulating HVEM [ JCI Insight, 2025, 10(18)e190716] PubMed: 40985894
Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies [ Cell Death Discov, 2025, 11(1):91] PubMed: 40055336

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。

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