Patupilone (Epothilone B)

製品コードS1364 バッチS136403

印刷

化学情報

Chemical Structure Synonyms EPO906 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H41NO6S
分子量 507.68 CAS No. 152044-54-7
Solubility (25°C)* 体外 DMSO 102 mg/mL (200.91 mM)
Ethanol 102 mg/mL (200.91 mM)
Water 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 Patupilone (EPO906, Epothilone B) is a paclitaxel-like microtubule-stabilizing agent with EC0.01 of 1.8 μM. Phase 2.
in vitro

Patupilone (Epothilone B) shows better activity than Epothilone A, with an EC0.01 of 1.8 μM. It potently inhibits cell proliferation in HCT116 cells, with IC50 of 0.8 nM. [1] This compound induces mitotic arrest and displays cytotoxicity in KB3-1, KBV-1, Hela, and Hs578T cells, with IC50 of 3 nM to 92 nM. It competes with Taxol in binding to microtubules, with IC50 of 3.3 μM. [2] In MCF-7 cells overexpressing GFP-α-tubulin, it (3.5 nM) efficiently blocks microtubule dynamics. Meanwhile, it induces mitotic arrest with IC50 of 3.5 nM. [3] In multiple myeloma (MM) cells, including RPMI 8226, U266, MM.1S, LR5, and MR20, it directly suppresses proliferation with IC50 of 1 nM to 10 nM. Similarly, it (10 nM) also induces cell cycle arrest and apoptosis. [4] A recent study reveals that, in ovarian cancer Hey cells, it (5 nM–100 nM) enhances surface epithelial cell adhesion antigen (EpCAM), without affecting the transcription or the total cellular level of EpCAM. [5]
in vivo

In a mouse xenograft model of RPMI 8226 cells, Patupilone (Epothilone B) (2.5 mg/kg–4 mg/kg) prolongs survival and suppresses tumor growth. [4] Similarly, this compound at the same dose also inhibits tumor growth in mouse xenograft models of prostate cancer cells, including DU145 and PC3. [6]

プロトコル(参考用のみ)

キナーゼアッセイ Tubulin polymerization assay
Calf brain microtubule proteins (MTP) are purified, which includes approximately 15%–20% microtubule associated proteins. The buffer (MES buffer) used for the Epothilone B-microtubule studies contains 0.1 M 2-morpholinoethanesulfonic acid (MES), 1 mM EGTA and 0.5 mM MgCl2 at pH 6.6. Samples for electron microscopy are placed on carbon-over-Parlodion-coated grids (300 mesh) and negatively stained with 2% uranyl acetate. Microtubule assembly in the presence or absence of Patupilone (Epothilone B) is monitored spectrophotometrically by using a spectrophotometer equipped with a thermostatically regulated liquid circulator. The temperature is held at 35 °C and changes in turbidity (representative of polymer mass) are monitored at 350 nm. Effective concentration (EC0.01), defined as the interpolated concentration capable of inducing an initial slope of 0.01 OD/min rate, is calculated using the formula EC0.01 = concentration/slope and expressed as the mean with standard deviation obtained from three different concentrations.
細胞アッセイ 細胞株 KB3-1, KBV-1, Hela, and Hs578T cells
濃度 0–1 μM
反応時間 72 hours
実験の流れ

For mitotic block and aberrant mitosis, cells are plated either in 48-well plates (for blue and cell counting) or onto coverslips. After 24 hours, they are treated with Patupilone (Epothilone B) and scored at regular intervals. For the cytotoxicity analysis, cells are counted and scored as blue positive or negative. Concurrently, coverslips and aliquots of cells in the culture supernatant are fixed and stained with Hoechst33342 in PBS. These cells are scored for cells blocked at the G2/M transition and aberrant mitosis.
動物実験 動物モデル Mice xenograft model of RPMI 8226 cells
投薬量 2.5 mg/kg–4 mg/kg
投与方法 Inject intravenously

参考

  • https://pubmed.ncbi.nlm.nih.gov/11506611/
  • https://pubmed.ncbi.nlm.nih.gov/7757983/
  • https://pubmed.ncbi.nlm.nih.gov/14522931/
  • https://pubmed.ncbi.nlm.nih.gov/15367426/
  • https://pubmed.ncbi.nlm.nih.gov/20674962/
  • https://pubmed.ncbi.nlm.nih.gov/15948135/
  • https://pubmed.ncbi.nlm.nih.gov/1672157/

カスタマーフィードバック

, , Oncotarget, 2015, 6(13):10893-907.

, , J Cancer Res Clin Oncol, 2016, 142(11):2281-9.

Data independently produced by , , Dr. Helen Sadik of Johns Hopkins University

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：

Rehabilitation enhances epothilone-induced locomotor recovery after spinal cord injury [ Brain Commun, 2023, 5(1):fcad005] PubMed: 36744011
A new form of axonal pathology in a spinal model of neuromyelitis optica [ Brain, 2022, awac079] PubMed: 35202467
Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures [ Genome Med, 2021, 13(1):189] PubMed: 34915921
Tubulin isotypes optimize distinct spindle positioning mechanisms during yeast mitosis [ J Cell Biol, 2021, 220(12)e202010155] PubMed: 34739032
Various effects of two types of kinesin-5 inhibitors on mitosis and cell proliferation [ Biochem Pharmacol, 2021, 193:114789] PubMed: 34582773
Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS [ Cell Rep Med, 2020, 1(9):100159] PubMed: 33377130
Deletion of Glutathione S-Transferase Omega 1 Activates Type I Interferon Genes and Downregulates Tissue Factor [ Cancer Res, 2020, canres.530.2020] PubMed: 32571799
Paclitaxel Enhances the Innate Immunity by Promoting NLRP3 Inflammasome Activation in Macrophages. [ Front Immunol, 2019, 10:72] PubMed: 30761140
CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance [ Sci Rep, 2019, 9(1):19384] PubMed: 31852908
Systemic administration of epothilone D improves functional recovery of walking after rat spinal cord contusion injury [Ruschel J, et al. Exp Neurol, 2018, 306:243-249] PubMed: 29223322

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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