体外活性：PRI-724 特异性结合 CBP，但不结合相关转录共激活因子 p300，从而破坏 CBP 与 β-catenin 的相互作用。 PRI-724 处理选择性诱导结肠癌细胞凋亡，但不诱导正常结肠上皮细胞凋亡，并减少结肠癌细胞的体外生长。激酶测定：双荧光素酶报告基因 (DLR) 测定系统提供了执行双报告基因测定的有效方法。在 DLRTM 检测中，从单个样品中依次测量萤火虫 (Photinuspyralis) 和海肾 (Renilla reniformis，也称为海三色堇) 荧光素酶的活性。首先通过添加荧光素酶检测试剂 II (LAR II) 来测量萤火虫荧光素酶报告基因，以产生“辉光型”发光信号。对萤火虫发光进行定量后，该反应被淬灭，并通过同时向同一管中添加 Stop & Glo® 试剂来启动海肾荧光素酶反应。 Stop & Glo® 试剂还会从海肾荧光素酶产生“发光型”信号，该信号在测量过程中缓慢衰减。在 DLRTM 检测系统中，两种报告基因均可产生具有亚阿托摩尔 (<10-18) 灵敏度的线性检测结果，并且在实验宿主细胞中任一报告基因均无内源活性。此外，DLRTM 检测的集成形式可对转染细胞或无细胞转录/翻译反应中的两种报告基因进行快速定量。细胞测定：用 ICG-001 或 IQ1 处理大鼠 EMC，并进行免疫共沉淀 (co-IP) 测定。用 DMSO、ICG-001 或 IQ1 处理细胞 24 小时。在 DMSO 对照处理的细胞中，基本上所有 β-连环蛋白都与 CBP 相关。 IQ1 治疗对 β-连环蛋白共激活剂的使用影响极小。然而，正如预期的那样，ICG-001 治疗减少了 β-连环蛋白/CBP 相互作用，同时增加了 β-连环蛋白/p300 相互作用。

PRI-724 在小鼠结肠癌异种移植模型中表现出抗肿瘤活性。 PRI-724的I期临床试验初步结果已公开披露。该药物表现出可接受的毒性特征，只有一种剂量限制性毒性，即 3 级可逆性高胆红素血症。 PRI-724 针对晚期骨髓恶性肿瘤患者的开放标签剂量递增 I/II 期研究仍在进行中。

Oncotarget.2019Apr 30;10(32):3013-3026;Transl Respir Med.2014 Sep 11;2:8;Am J Cancer Res.2015 Jul 15;5(8):2344-60.

C33H35N6O7P

658.64

1422253-38-0

1422253-38-0 (PRI-724);1198780-38-9 847591-62-2 (deleted);780757-88-2 (ICG001);

P(=O)(O)(O)OC1C=CC(=CC=1)C[C@H]1C(N(CC2=CC=CC3C=CC=NC2=3)[C@@H](C)[C@]2([H])N(C(NCC3C=CC=CC=3)=O)N(C)CC(N21)=O)=O

(6S,9aS)-N-benzyl-6-(4-hydroxybenzyl)-8-(naphthalen-1-ylmethyl)-4,7-dioxooctahydro-1H-pyrazino[1,2-a]pyrimidine-1-carboxamide

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。