Veliparib (ABT-888) is a potent PARP inhibitor, inhibiting PARP1 and PARP2 with K_is of 5.2 and 2.9 nM, respectively^[1].

Veliparib (ABT-888) is also tested against SIRT2, an enzyme that also uses NAD⁺ for catalysis, and found to be inactive (>5,000 nM). The receptor profile of Veliparib is determined in a panel of 74 receptor-binding assays at a concentration of 10 μM. Veliparib displaces control-specific binding at 50% or greater at the human H₁(61%), the human 5-HT_1A (91%), and the human 5-HT₇ (84%) sites only. The IC₅₀s for these three receptors are 5.3, 1.5, and 1.2 μM, respectively^[1]. c-Met knockdown cells show 4.2- (shMet-A; 95% CI=4-4.5) or 4.6-fold (shMet-B; 95% CI=4.4-4.8) growth inhibition when treated with 60 μM Veliparib (ABT-888). When treated with 38 μM Veliparib, c-Met knockdown cells show 2- (shMet-A; 95% CI=1.5-2.5) or 1.9-fold (shMet-B; 95% CI=1.3-2.5) growth inhibition^[2]. In HaCaT cells, at 6 h post-treatment by Veliparib (ABT-888), cell viability is significantly increases under 1,000 µM sulfur mustard (SM) exposure, whereas Veliparib does not protect cell viability under 100 µM SM exposure. Moreover, the addition of Veliparib no longer shows the protective effect at 24 h post SM exposure^[3].

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.

Veliparib (ABT-888) is a potent inhibitor of PARP, has good oral bioavailability, can cross the blood-brain barrier in syngeneic and xenograft tumor models^[1]. In MDA-MB-231 xenograft tumor models, combination treatment (AG014699/PF-02341066 and Veliparib (ABT-888)/Foretinib) substantially reduced tumor growth compared to either inhibitor alone^[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.

244.29

C₁₃H₁₆N₄O

912444-00-9

维利帕尼

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 29 mg/mL (118.71 mM)

* “≥” means soluble, but saturation unknown.

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： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (8.51 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (8.51 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 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

• 2.

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

  Solubility: ≥ 2.08 mg/mL (8.51 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (8.51 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (8.51 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (8.51 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Donawho CK, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007 May 1;13(9):2728-37.

  [2]. Du Y, et al. Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors. Nat Med. 2016 Feb;22(2):194-201.

  [3]. Liu F, et al. Effects of poly (ADP-ribose) polymerase-1 (PARP-1) inhibition on sulfur mustard-induced cutaneous injuries in vitro and in vivo. PeerJ. 2016 Apr 4;4:e1890.

PARP1 enzyme activity is measured by using a commercial assay kit with the exception that cell lysates containing wild-type PARP1 or PARP Y907 mutant are used in place of the PARP1 protein included with the kit. Total lysate (500 ng) is added to each reaction. The dose course of PARP inhibitor Veliparib (ABT-888) is from 0.01 to 1,000 μM. PARP enzyme activity of wild-type and mutants is determined after incubation with the substrate is measured using a plate reader^[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.

Cell viability is quantified using the Cell Counting Kit-8 (CCK-8). This assay is based on Dojindo’s highly water-soluble tetrazolium salt. WST-8 is reduced by dehydrogenases in cells to give an orange, water-soluble formazan dye. The amount of the formazan dye generated by dehydrogenases in cells is directly proportional to the number of living cells. Briefly, exponentially growing HaCaT cells are seeded in 96-well plates at a density of 10,000 cells/well. 6 h or 24 h after exposure to sulfur mustard (SM) and the administration of Veliparib, the CCK-8 reagent is added^[3.

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]
MDA-MB-231 (0.5×10⁶), HCC1937 (2×10⁶) or MCF-7 (5×10⁶) cells are injected into the mammary fat pads of female nude (Swiss Nu/Nu) mice of 6-8 weeks of age. A1034 (0.5×10⁶) cells are injected into the mammary fat pads of female FVB/NJ mice of 6-8 weeks of age. H1993 (0.5×10⁶) cells are injected subcutaneously into the right flank of female nude (Swiss Nu/Nu) mice of 6-8 weeks of age. When the tumor volume reaches 50 mm³, PF-02341066 (5 mg/kg) and Foretinib (5 mg/kg), AG014699 (5 mg/kg) and Veliparib (25 mg/kg), dissolved in aqueous 50 mM sodium acetate, pH 4, are administered to mice five times per week as single agents or in combination for the number of days specified in the figure legend. Tumor is measured at the indicated time points, and tumor volume is calculated by the formula: π/6×length×width². For MDA-MB-231 and A1034 xenograft mouse models, mice are imaged before and after treatment using the IVIS Imaging System to assess tumor growth. Mice are injected with 100 μL of D-luciferin (15 mg/mL in PBS).

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]. Donawho CK, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007 May 1;13(9):2728-37.

  [2]. Du Y, et al. Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors. Nat Med. 2016 Feb;22(2):194-201.

  [3]. Liu F, et al. Effects of poly (ADP-ribose) polymerase-1 (PARP-1) inhibition on sulfur mustard-induced cutaneous injuries in vitro and in vivo. PeerJ. 2016 Apr 4;4:e1890.