TCS PrP Inhibitor 13   中文名称: TCS PrP抑制剂13

IC50: 3 nM (PrPC in ScN2a and F3 cells)[1]

TCS PrP Inhibitor 13（0~500 μM；神经鞘瘤细胞）显着提高裂解的 caspase-3 的表达，同时显着降低总 ERK1/2、pAKT、总 FAK、Cyclin D1 和 PrPC 的水平。 TCS PrP 抑制剂 13（神经鞘瘤细胞）可显着减少细胞总数和增殖的 Ki67 阳性细胞的数量[2]。

为了寻找有效的抗朊病毒化合物，研究人员合成并评价了各种吡唑酮衍生物。19种化合物中有7种对PrP-res的积累有抑制作用，其中活性显著的化合物13在ScN2a和F3细胞系中的IC50值均为3 nM。理化和生化性质的研究结果表明，这些化合物的作用机制与任何抗氧化活性、任何羟基自由基清除活性或任何类sod活性无关。[1]

[1]. Kimata A, et al. New series of antiprion compounds: pyrazolone derivatives have the potent activity of inhibiting protease-resistant prion protein accumulation [published correction appears in J Med Chem. 2008 Mar 13;51(5):1503]. J Med Chem. 2007;50(21):5053-5056.
[2]. Provenzano L, et al. Cellular prion protein (PrPC) in the development of Merlin-deficient tumours. Oncogene. 2017;36(44):6132-6142.

Loss of function mutations in the neurofibromatosis Type 2 (NF2) gene, coding for a tumour suppressor, Merlin, cause multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas. These tumours may occur sporadically or as part of the hereditary condition neurofibromatosis Type 2 (NF2). Current treatment is confined to (radio) surgery and no targeted drug therapies exist. NF2 mutations and/or Merlin inactivation are also seen in other cancers including some mesothelioma, breast cancer, colorectal carcinoma, melanoma and glioblastoma. To study the relationship between Merlin deficiency and tumourigenesis, we have developed an in vitro model comprising human primary schwannoma cells, the most common Merlin-deficient tumour and the hallmark for NF2. Using this model, we show increased expression of cellular prion protein (PrPC) in schwannoma cells and tissues. In addition, a strong overexpression of PrPC is observed in human Merlin-deficient mesothelioma cell line TRA and in human Merlin-deficient meningiomas. PrPC contributes to increased proliferation, cell-matrix adhesion and survival in schwannoma cells acting via 37/67 kDa non-integrin laminin receptor (LR/37/67 kDa) and downstream ERK1/2, PI3K/AKT and FAK signalling pathways. PrPC protein is also strongly released from schwannoma cells via exosomes and as a free peptide suggesting that it may act in an autocrine and/or paracrine manner. We suggest that PrPC and its interactor, LR/37/67 kDa, could be potential therapeutic targets for schwannomas and other Merlin-deficient tumours.[2]

C15H11N3O3

281.27

281.08

C, 64.05; H, 3.94; N, 14.94; O, 17.06

34320-83-7

2750328

White to yellow solid powder

1.4±0.1 g/cm3

445.1±47.0 °C at 760 mmHg

223.0±29.3 °C

0.0±1.1 mmHg at 25°C

1.674

1.92

78.49

0

4

2

21

444

0

O=C1CC(C2C=CC(=CC=2)[N+](=O)[O-])=NN1C1C=CC=CC=1

FDAVFKZPGQEGDX-UHFFFAOYSA-N

InChI=1S/C15H11N3O3/c19-15-10-14(11-6-8-13(9-7-11)18(20)21)16-17(15)12-4-2-1-3-5-12/h1-9H,10H2

5-(4-nitrophenyl)-2-phenyl-4H-pyrazol-3-one

TCS PRP INHIBITOR 13; 34320-83-7; 5-(4-nitrophenyl)-2-phenyl-4H-pyrazol-3-one; 3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-5(4H)-one; 3-(4-Nitrophenyl)-1-phenyl-2-pyrazolin-5-one; 2,4-DIHYDRO-5-(4-NITROPHENYL)-2-PHENYL-3H-PYRAZOL-3-ONE; 5-(4-nitrophenyl)-2-phenyl-2,4-dihydro-3H-pyrazol-3-one; ST51035799;

2934.99.9001

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)

DMSO : 100 mg/mL (355.53 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (8.89 mM) (饱和度未知) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80+，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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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。