Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a K_i of less than 0.01 nM. Venetoclax induces autophagy^[1][2][3].

Venetoclax (ABT-199) potently kills FL5.12-BCL-2 cells (EC₅₀=4 nM), Venetoclax (ABT-199) shows much weaker activity against FL5.12-BCL-XL cells (EC₅₀=261 nM). ABT-199 also shows selectivity in cellular mammalian two-hybrid assays, where it disrupts BCL-2-BIM complexes (EC₅₀=3 nM) but is much less effective against BCL-XL-BCL-XS (EC₅₀=2.2 μM) or MCL-1-NOXA complexes^[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.

After a single oral dose of 12.5 mg per kg body weight in xenografts derived from RS4;11 cells (ALL), Venetoclax (ABT-199) causes a maximal tumor growth inhibition (TGI_max) of 47% (P<0.001) and tumor growth delay (TGD) of 26% (P<0.05)^[1].
Treatment of established xenografted (a mouse xenograft model of the T-ALL cell line LOUCY) tumors with Venetoclax (ABT-199) 100 mg/kg for 4 days results in a significant reduction of leukemic burden^[2].

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.

868.44

C₄₅H₅₀ClN₇O₇S

1257044-40-8

维奈妥拉

Room temperature in continental US; may vary elsewhere.

DMSO : 77.5 mg/mL (89.24 mM; Need ultrasonic)

Ethanol : < 1 mg/mL (insoluble)

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。

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： 60% phosal 50 propylene glycol (PG), 30% polyethylene glycol 400 (PEG400), 10% ethanol

  Solubility: 20 mg/mL (23.03 mM); Suspended solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

  Solubility: ≥ 5.25 mg/mL (6.05 mM); Clear solution
• 3.

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

  Solubility: ≥ 2.58 mg/mL (2.97 mM); Clear solution

  此方案可获得 ≥ 2.58 mg/mL (2.97 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.8 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

• 4.

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

  Solubility: 2.5 mg/mL (2.88 mM); Suspended solution; Need ultrasonic and warming

  此方案可获得 2.5 mg/mL (2.88 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 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]. Souers AJ, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.

  [2]. Peirs S, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014 Dec 11;124(25):3738-47.

  [3]. Bi C, et al. Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. Haematologica. 2017 Apr;102(4):755-764.

RS4;11 cells are seeded at 50,000 per well in 96-well plates and treated with compounds diluted in half-log steps starting at 1 μM and ending at 0.00005 μM. All other leukemia and lymphoma cell lines are seeded at 15,000-20,000 cells per well in the appropriate medium and incubated with Venetoclax or Navitoclax for 48 h. Effects on proliferation are determined using Cell TiterGlo reagent. EC₅₀ values are determined by nonlinear regression analysis of the concentration-response data. Mouse FL5.12-BCL-2 and FL5.12-BCL-XL cells are propagated and assessed. Bak^-/- Bax^-/- double knockout mouse embryonic fibroblasts are seeded into 96-well microtiter plates at 5,000 cells per well in DMEM supplemented with 10% FBS. Venetoclax (ABT-199) in the same culture medium is added in half-log dilutions starting at 5 μM. The cells are then incubated at 37°C (5% CO₂) for 48 h, and the effects on proliferation are determined using Cell TiterGlo reagent^[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.

Mice^[2]
Nonobese diabetic/severe combined immunodeficient γ (NSG) mice are injected at 6 weeks of age in the tail vein with 150 µL phosphate-buffered saline containing 5×10⁶ luciferase-labeled LOUCY cells. At regular time points, the bioluminescence is measured using the IVIS Lumina II imaging system. At 6 weeks, the cells are engrafted and the mice are randomly divided into 2 groups (with an equal number of males and females in both groups), and the treatment is started on day 0. Mice are treated with Venetoclax (ABT-199) 100 mg/kg body weight or with vehicle via oral gavage for 4 consecutive days. At days 0, 2, and 4 the bioluminescene is measured.

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]. Souers AJ, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.

  [2]. Peirs S, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014 Dec 11;124(25):3738-47.

  [3]. Bi C, et al. Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. Haematologica. 2017 Apr;102(4):755-764.