| Powder: -20°C for 3 years | In solvent: -80°C for 2 years
Navitoclax 是有效,可口服的Bcl-2抑制剂,可与Bcl-xL,Bcl-2, Bcl-w 等多种Bcl-2家族蛋白结合,Ki 值小于 1 nM。
产品描述 | Navitoclax (ABT-263) is a potent, orally bioavailable Bcl-2 family protein inhibitor that avidly binds Bcl-2, Bcl-xL, and Bcl-W (Ki < 1 nM for all three proteins). |
靶点活性 | Bcl-W:<1 nM (Ki, cell free), Bcl-xL:0.4 nM (Ki, cell free), Bcl-2:<1 nM (Ki, cell free) |
体外活性 | ABT-263 is a potent, orally bioavailable Bad-like BH3 mimetic (K(i)'s of <1 nmol/L for Bcl-2, Bcl-xL, and Bcl-w). In human tumor cells, ABT-263 induces Bax translocation, cytochrome c release, and subsequent apoptosis [1]. ABT-263 was active against approximately one-half of the cell lines of the PPTP in vitro panel [2]. |
体内活性 | The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia [1]. ABT-263 induced significant prolongation of the EFS distribution in 9 of 35 (26%) of the solid tumor xenografts and in 5 of 6 (83%) of the evaluable ALL xenografts [2]. ABT-263 exhibited a range of antitumor activity, leading to complete tumor regression in several models. Significant regressions of tumors as large as 1 cc were also observed. The efficacy of ABT-263 was also quite durable; in several cases, minimal tumor regrowth was noted several weeks after the cessation of treatment [3]. |
激酶实验 | ABT-737 and ABT-263 were synthesized as previously described. The enantiomer and BH3-only peptides were synthesized at Abbott. Binding affinities (Ki or IC50) were determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs were used: f-bad (1 nmol/L) and Bcl-xL (6 nmol/L), f-Bax (1 nmol/L) and Bcl-2 (10 nmol/L), f-Bax (1 nmol/L) and Bcl-w (40 nmol/L), f-Noxa (2 nmol/L) and Mcl-1 (40 nmol/L), and f-Bax (1 nmol/L) and Bcl-2-A1 (15 nmol/L). Binding affinities for Bcl-xL were also determined using a time-resolved fluorescence resonance energy transfer assay. Bcl-xL (1 nmol/L, His tagged) was mixed with 200 nmol/L f-Bak, 1 nmol/L Tb-labeled anti-His antibody, and compound at room temperature for 30 min. Fluorescence was 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. Dissociation constants (Ki) were determined using Wang's equation [1]. |
细胞实验 | Human tumor cell lines were maintained at 37°C containing 5% CO2. SCLC cell lines were cultured in RPMI 1640 with 10% fetal bovine serum (FBS), 1% sodium pyruvate, 25 mmol/L HEPES, 4.5 g/L glucose, and 1% penicillin/streptomycin. Leukemia and lymphoma cell lines were cultured in RPMI 1640 supplemented with 10% FBS and 1% penicillin/streptomycin. Cells (1 × 10^4–5 × 10^4) were treated for 48 h in 96-well culture plates in a final volume of 100 μL and cytotoxicity was assessed with the CellTiter Glo assay [1]. |
动物实验 | C.B.-17 scid-bg or C.B.-17 scid mice were implanted with 5 × 10^6 (1 × 10^6 for DoHH2) cells in 0.2 mL 50% Matrigel s.c. into the right flank. Tumor-bearing mice were size matched (~235 mm3; day 0) into treatment and control groups, ear tagged, and monitored individually. Tumor volume was measured two to three times weekly by electronic calipers (volume = length × width2 / 2). Tumor growth inhibition was calculated based on the difference in mean tumor volumes between treated and appropriate vehicle control groups. Partial response (PR) is defined as ≥50% tumor growth inhibition, and complete response (CR) is defined as nonpalpable tumor. All studies used 8 to 10 mice per group. ABT-263 was formulated in 10% ethanol, 30% polyethylene glycol 400, and 60% Phosal 50 PG and administered p.o. The other agents used [rituximab, doxorubicin, cyclophosphamide, vincristine, bortezomib, and prednisone] were administered i.p., p.o., or i.v. and formulated according to the manufacturers' recommendations. For combination studies, ABT-263 was given ~2 h before the other agents, except bortezomib, which was given ~4 h before ABT-263 [1]. |
别名 | ABT-263 |
化合物与蛋白结合的复合物 |
Bcl_2-Navitoclax (ABT-263) Complex |
分子量 | 974.61 |
分子式 | C47H55ClF3N5O6S3 |
CAS No. | 923564-51-6 |
| Powder: -20°C for 3 years | In solvent: -80°C for 2 years
Ethanol: <1 mg/mL
DMSO: 200 mg/mL (205.21 mM), Need ultrasonic
H2O: <1 mg/mL
( < 1 mg/mL refers to the product slightly soluble or insoluble )
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
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您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
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