Navitoclax (ABT-263)

製品コードS1001 バッチS100130

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

C47H55ClF3N5O6S3
分子量 974.61 CAS No. 923564-51-6
Solubility (25°C)* 体外 DMSO 100 mg/mL (102.6 mM)
Water Insoluble
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 ナビトクラックス (Navitoclax (ABT-263)) は Bcl-xL, Bcl-2 and Bcl-w の強力な阻害剤であり、阻害定数は cell-free assay において Ki ≦ 0.5 nM, 1 nM および 1nM です。一方、Mcl-1 および A1 に対しては比較的弱い結合力を示します。臨床第2相試験中
in vitro Navitoclax (ABT-263) is structurally related to ABT-737 and acts as a disruptor of Bcl-2/Bcl-xL interactions with pro-apoptotic proteins. Overexpression of the prosurvival Bcl-2 family members is commonly associated with tumor maintenance, progression, and chemoresistance. [1] This compound displays the protection afforded by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively. [1] A wide range of cellular activity is observed with it having a 50% growth inhibition (EC50) of 110 nM against the most sensitive line (H146), whereas its activity in the least sensitive line (H82) results in an EC50 at 22 μM. All four cell lines with EC50 values of <400 nM (H146, H889, H1963, and H1417) are also highly sensitive to ABT-737, and the two most resistant lines (H1048 and H82) are similarly resistant to ABT-263. [2]
in vivo When administered at 100 mg/kg/day in the H345 xenograft model, Navitoclax (ABT-263) demonstrates significant antitumor efficacy with 80% TGI and 20% of treated tumors indicating at least a 50% reduction in tumor volume. [2] Oral administration of this compound alone causes complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. [2] In xenograft models of aggressive B-cell lymphoma and multiple myeloma where it displays modest or no single agent activity, ABT-263 significantly enhances the efficacy of clinically relevant therapeutic regimens. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Affinity determination
Binding affinities (Ki or IC50) of Navitoclax (ABT-263) against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM), f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM), and f-Bax (1 nM) and Bcl-2-A1 (15 nM). Its binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and this compound at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters.
細胞アッセイ 細胞株 SCLC cell lines
濃度 0-1 μM
反応時間 48 hours
実験の流れ

Human tumor cell lines SCLC cell lines are maintained at 37℃ containing 5% CO2. SCLC cell lines are cultured in RPMI 1640 with 10% fetal bovine serum (FBS), 1% sodium pyruvate, 25 mM HEPES, 4.5 g/L glucose, and 1% penicillin/streptomycin. Leukemia and lymphoma cell lines are cultured in RPMI 1640 supplemented with 10% FBS and 1% penicillin/streptomycin. Cells (1-5×10 4) are treated by Navitoclax (ABT-263) for 48 hours in 96-well culture plates in a final volume of 100 μL and cytotoxicity is assessed with the CellTiter Glo assay. In vitro cyto toxicity of this compound is assayed.
動物実験 動物モデル C.B.-17 scid-bg or C.B.-17 scid mice
投薬量 100 mg/kg/d
投与方法 Administered via p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/18451170/
  • https://pubmed.ncbi.nlm.nih.gov/18519752/

カスタマーフィードバック

Data from [PLoS One, 2011, 6, e21980]

Data from [PLoS One, 2011, 6, e21980]

Data from [PLoS One, 2011, 6, e21980]

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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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