YCH1899

PARP-1 <0.001 nM (IC50) PARP-2 <0.001 nM (IC50) PARP3 1.1 nM (IC50) PARP4 1.0 nM (IC50) TNKS1 3.8 nM (EC50) TNKS2 12.4 nM (IC50) PARA6 9.5 nM (IC50) PARP-7 7.3 nM (IC50) ARTD10/PARP10 10.8 nM (IC50) PARA11 2.166 μM (IC50) human PARP12 14.1 nM (IC50) PARP14 35.914 μM (IC50) PARP15 51.623 nM (IC50)

在 Capan-1、Capan-1/OP 和 Capan-1/TP 细胞上，YCH1899（7 天）表现出强烈的抗增殖作用，IC50 值分别为 0.10、0.89 和 1.13 nM [1]。 YCH1899（0.001-1 nM，4 小时）抑制 PARP 产生，同时稳定 PARP1-DNA 复合物 [1]。 YCH1899 (3.5 h) 抑制 BRCA 突变型/野生型细胞（V-C8、V79、HCT-15 和 HCC1937）的生长，IC50 范围为 1.19 至 44.24 nM[1]。 Capan-1、Capan-1/OP 和 Capan-1/TP 细胞暴露于 1 μM YCH1899 24 小时，会导致 DNA 损伤并显着增加 γH2AX 的量 [1]。当以 1 μM 浓度给药 48 小时时，YCH1899 显着降低 U2OS-DR-GFP 细胞中同源重组 (HR) 的修复活性 [1]。

在大鼠中，YCH1899（5 mg/kg，静脉注射）表现出中等的清除能力[1]。在异种移植小鼠肿瘤模型中，MDA-MB-436/OP（6.25、12.5 和 25 mg/kg，每天口服一次，持续 27 天）和 Capan-1/R（12.5 和 25 mg/kg）中的 YCH1899 ，每天口服一次，持续 21 天）克服了 Talazoparib 耐药性并显着减小了肿瘤体积 [1]。

细胞增殖检测[1]
细胞类型： HCC1937、HCT-15、MDA-MB-436、UWB1.289、UWB1.289+BRCA1、V–C8、V79 细胞
测试浓度：约0-1 μM
孵育时间：24小时
实验结果：抑制BRCA缺陷型细胞的增殖/野生型细胞和IC50值分别为4.54、44.24、0.52、0.02、0.34、1.19、29.32nM。

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免疫荧光[1]
细胞类型： Capan-1、Capan-1/OP 细胞、Capan-1/TP 细胞
测试浓度： 0.01, 0.1, 1 μM
孵育时间： 24 小时
实验结果： γH2AX 水平以剂量依赖性方式增加。

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蛋白质印迹分析[1]
细胞类型： Capan-1 和 Capan-1/ OP 细胞
测试浓度： 1、 10, 100 nM
孵育时间： 4 小时
实验结果： 提高 PARP1-DNA 复合物的稳定性，并在存在以下物质时诱导染色质结合的 PARP1 积累MMS（甲磺酸盐）。 0.1% H2O2 存在时抑制 PARP 形成。

Animal/Disease Models: MDA-MB-436/OP xenografts and Capan-1/R-in vivo xenografts mice[1]
Doses: 12.5 and 25 mg/kg
Route of Administration: Oral administration
Experimental Results: Inhibited MDA-MB-436/OP xenografts tumor growth with T/C of 36.74% and 15.29% at 12.5 and 25 mg/kg Inhibited Capan-1/R xenografts tumor growth with T/C of 48.92% and 13.87% at 12.5 and 25 mg/kg.

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Animal/Disease Models: rats[1 ]
Doses: 5 mg/kg
Route of Administration: intravenous (iv) injection
Experimental Results: Had a moderate clearance rate (24.5 mL/min/kg) and half-life (3.25 h).

[1]. Sun Y, et al. YCH1899, a Highly Effective Phthalazin-1(2H)-one Derivative That Overcomes Resistance to Prior PARP Inhibitors. J Med Chem. 2023 Aug 21.

C25H18BRFN6O3

549.35

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。