A-385358 is a selective inhibitor of Bcl-X_L with K_is of 0.80 and 67 nM for Bcl-X_L and Bcl-2, respectively.

A-385358 is a selective inhibitor of Bcl-X_L with K_is of 0.80 and 67 nM for Bcl-X_L and Bcl-2, respectively, in fluorescence polarization assays. Treatment of IL-3-deprived FL5.12/Bcl-X_L cells for 24 hours with A-385358 results in cell killing with an EC₅₀ of 0.47±0.05 μM (n=68). This effect is accompanied by an increase in caspase-3 activity. Consistent with the greater affinity for the Bcl-X_L versus Bcl-2 hydrophobic grooves, the EC₅₀ of A-385358 for IL-3-depleted FL5.12/Bcl-2 cells (1.9±0.1 μM; n=55) is 4-fold higher relative to the cytokine-deprived FL5.12/Bcl-X_L cells. In addition, A-385358 is more effective at stimulating cytochrome c release from mitochondria isolated from FL5.12/Bcl-X_L versus Bcl-2 cells^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

The combination of A-385358 given at 100 mg/kg/d plus the lower dose of paclitaxel produces a significant reduction in tumor growth (%T/C) compare with paclitaxel monotherapy. This combination also yields a >100% increase in time for tumors to reach 900 mm³ (%ILS) compare with vehicle control. Maximal efficacy is observed during the dosing period for A-385358, with slow but steady increase in the tumor growth after termination of treatment. The combination of A-385358 at 75 mg/kg/d plus paclitaxel at 30 mg/kg/d is also well tolerated and inhibits tumor growth rate by nearly 80%. Significant effects on tumor growth relative to paclitaxel monotherapy are observed with doses as low as 50 mg/kg/d^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

639.83

C₃₂H₄₁N₅O₅S₂

406228-55-5

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 50 mg/mL (78.15 mM; Need ultrasonic)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: 2.5 mg/mL (3.91 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (3.91 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (3.91 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.91 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Shoemaker AR, et al. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res. 2006 Sep 1;66(17):8731-9.

FL5.12 cells suspended in EMB growth medium containing 4% fetal bovine serum (FBS) are incubated at 37°C for 1 hour in 10 μM A-385358. Compound concentration is determined by high-performance liquid chromatography before and after the 1-hour incubation following brief centrifugation. To analyze membrane-bound fractions following compound incubation, cells are washed once with 10 volumes of cold PBS and lysed with 4 mL of water. A-385358 concentration is determined from aliquots of lysate before and after centrifugation^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

A549 cells (1×10⁵) are plated in 96-well plates in medium containing 10% fetal bovine serum. Following attachment, A-385358 is added to one set of wells (final concentration of 50 μM in 10% FBS) and medium is added to another set. [³H]Paclitaxel (5 μM; 0.5 μCi/mL final concentration) is added to all wells and the cells are incubated at 37°C for various periods of time. For washout experiments, cells are exposed first to [³H]paclitaxel for 2 hours. The cells are washed once with medium and then incubated with fresh medium with or without 50 μM A-385358 at 37°C for various periods of time^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

For efficacy studies, male CD-1 nude mice are inoculated with a 1:5 dilution of tumor brei in 50% Matrigel and analysis is conducted. A-385358 is delivered in a vehicle containing 5% Tween 80, 20% propylene glycol, and 75% PBS (pH 3.8). Paclitaxel is formulated according to the recommendations of the manufacturer. For combination therapy of paclitaxel plus A-385358, both drugs are administered i.p. with the paclitaxel given several hours before treatment with A-385358 (except for immunohistochemistry studies looking at expression of MPM-2 and caspase-3 wherein the two drugs are given simultaneously)^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Shoemaker AR, et al. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res. 2006 Sep 1;66(17):8731-9.