Pifithrin-α hydrobromide is a p53 inhibitor which blocks its transcriptional activity and prevents cells from apoptosis. Pifithrin-α hydrobromide is also an aryl hydrocarbon receptor (AhR) agonist.

p53^[1]
AhR^[2]

Pifithrin-α (PFT-α) hydrobromideis a water-soluble compound that could suppress p53 protein transcription. Pifithrin-α can suppress glucose oxidase (GOX)-induced p53 protein increase in whole cell lysates, but cyclosporine A (CsA) fails to show such an inhibition effect. Notably, Pifithrin-α is able to block the GOX-induced Bcl-2 protein reduction. Similarly, it is Pifithrin-α rather than CsA that able to prevent the Bax increasing in whole cell lysates^[1]. Pifithrin-α inhibits p53-dependent apoptosis through an undetermined mechanism. Pifithrin-α also acts as an aryl hydrocarbon receptor (AhR) agonist and. Pifithrin-α is a potent AhR agonist as determined by its ability to bind the AhR, induce formation of its DNA binding complex, activate reporter activity, and up-regulate the classic AhR target gene CYP1A1^[2].

When the experiment is performed with Pifthirin-α (PFT-α) hydrobromide, a pharmacological p53 inhibitor, the percentage of annexin V-positive Foxe3^-/- SMCs decreases to WT levels. Pifithrin-α (2.2 mg/kg, i.p.) significantly reduces the incidence of aortic rupture and intramural hematomas in Foxe3^-/- mice that underwent transverse aortic constriction (TAC) (50% to 17%, P<0.05). After Pifthirin-α treatment, the mean diameter of the ascending aorta and the percentage of TUNEL-positive cells in the aortic media are also normalized to WT levels in surviving Foxe3^-/- animals (P<0.05)^[3].

367.30

Solid

C₁₆H₁₉BrN₂OS

63208-82-2

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : ≥ 50 mg/mL (136.13 mM)

H₂O : 1.25 mg/mL (3.40 mM; Need ultrasonic)

* "≥" 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 (sealed storage, away from moisture)。-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: ≥ 2.5 mg/mL (6.81 mM); Clear solution

   

  此方案可获得 ≥ 2.5 mg/mL (6.81 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 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。

• 2.

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

  Solubility: ≥ 2.5 mg/mL (6.81 mM); Clear solution

   

  此方案可获得 ≥ 2.5 mg/mL (6.81 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。

• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.81 mM); Clear solution

   

  此方案可获得 ≥ 2.5 mg/mL (6.81 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Yu W, et al. Cyclosporine A Suppressed Glucose Oxidase Induced P53 Mitochondrial Translocation and Hepatic Cell Apoptosis through Blocking Mitochondrial Permeability Transition. Int J Biol Sci. 2016 Jan 1;12(2):198-209.  [Content Brief]

  [2]. Hoagland MS, et al. The p53 Inhibitor Pifithrin-α Is a Potent Agonist of the Aryl Hydrocarbon Receptor. J Pharmacol Exp Ther. 2005 Aug;314(2):603-10.  [Content Brief]

  [3]. Kuang SQ, et al. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Invest. 2016 Mar 1;126(3):948-61.  [Content Brief]