Y-320 是一种口服有效的苯吡唑苯胺免疫调节剂。Y-320 抑制 IL-15 刺激的 CD4 T 细胞产生 IL-17, 其IC50值为 20-60 nM。Y-320 增强 G418 对 TP53、DMD和COL17A1 PTC 的读入,增加细胞蛋白质水平和蛋白质合成。Y-320 与低剂量 Paclitaxel (HY-B0015) 通过诱导 G2/M 期阻滞和细胞凋亡 (apoptosis) 显著致敏多药耐药性 (MDR) 肿瘤。Y-320 可用于类风湿关节炎 (RA) 和肿瘤的研究。
生物活性 | Y-320 is a potent, orally active phenylpyrazoleanilide immunomodulator. Y-320 inhibitsIL-17production byCD4T cells stimulated withIL-15withIC50values of 20 to 60 nM. Y-320 enhances TP53, DMD, and COL17A1 PTC readthrough by G418 and increases cellular protein levels and protein synthesis. Y-320 concomitants use of with a low dose ofPaclitaxel(HY-B0015) significantly sensitized multidrug resistance (MDR) tumors by inducing G2/M phase arrest andapoptosis. Y-320 can be used for research of rheumatoid arthritis (RA) andcancer[1][2][2]. |
IC50& Target[1] | |
体外研究 (In Vitro) | Y-320 (0-100 nM; 48 h) inhibits IL-17 production by murine and human CD4 T Cells stimulated with IL-15 with IC50values of 25.7, 52.4 and 57.4 nM for murine CD4 T cells, murine Th17 cells and human CD4 T cells, respectively[1]. Y-320 (0-100 nM; 48 h) inhibits phosphorylation of JAK1/JAK3 in murine CD4 T cells stimulated with IL-15/CXCL12/anti-CD3 mAb[1]. Y-320 (0.25-2 μM; 48 h) enhances PTC readthrough by G418 in different cell lines[2]. Y-320 (0-2 μM; 48 h; HDQ-P1 cells) increases cellular protein levels and ribosome biogenesis in a concentration-dependent manner[2]. Y-320 (0-2 μM; 48 h; Tsc2-/-cells) causes a small decrease in phospho-S6K combination with G418 (100 μM)[2]. Y-320 (1 μM; 48 h; HDQ-P1 cells) up-regulates CXC chemokine expression including CXCL10, CXCL8, and CXCL2[2]. Y-320 (500 nM; 72 h) reverses the resistance to paclitaxel in MDR cancer cells. Y-320 has the reversal index (RI) combined with Paclitaxel (0-1000 nM) are 5.5 (Bads-200), 9.4 (Bats-72) and 1.7 (Huh7-TS-48)[3]. Y-320 (500 nM; 72 h; Bads-200 cells) enhances Paclitaxel-induced G2/M arrest and enhances Paclitaxel-induced (500 nM) tumor cell apoptosis[3]. Y-320 (0-20 μM; 72 h; Bads-200 cells) is a substrate of P-gp reverses MDR by inhibiting P-gp function[3].
Cell Cycle Analysis[3] Cell Line: | Bads-200 cells | Concentration: | 500 nM | Incubation Time: | 72 hours | Result: | Increased the percentage of cells at G2/M phase, from 6.3% to 42.5%. |
Apoptosis Analysis[3] Cell Line: | Bads-200 cells | Concentration: | 500 nM | Incubation Time: | 72 hours | Result: | Increased the ratio of apoptotic Bads-200 cells (30.8% versus 2.2%). |
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体内研究 (In Vivo) | Y-320 (0-3 mg/kg; p.o.; daily, for 42 d) ameliorates collagen-induced arthritis (CIA) in DBA/1J mice with a reduction of IL-17 mRNA in arthritic joints[1]. Y-320 (5 mg/kg; i.v.; every three days, for 18 d; Homozygous nude athymic mice with Bats-72 xenograft) sensitizes MDR xenograft tumor to Paclitaxel in vivo[3].
Animal Model: | Type II collagen-induced arthritis (CIA) in DBA/1J mice[1] | Dosage: | 0, 0.1, 0.3, 1, and 3 mg/kg | Administration: | Oral administration; daily, for 42 days | Result: | Inhibited the development of CIA and the increase in paw thickness in a dose-dependent manner. Inhibited joint destructions in a dose-dependent manner. Improved inflammation and damage in the arthritic ankle joints in CIA mice.
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Animal Model: | Homozygous nude athymic mice with Bats-72 xenograft (female, 4-5 weeks old)[3] | Dosage: | 5 mg/kg; Paclitaxel (5 mg/kg) | Administration: | Intravenous injection; every three days, for 18 days | Result: | Inhibited tumor growth in Bats-72 xenografts without severe adverse effects. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 5.5 mg/mL(10.89 mM;Need ultrasonic) 配制储备液 1 mM | 1.9802 mL | 9.9008 mL | 19.8016 mL | 5 mM | 0.3960 mL | 1.9802 mL | 3.9603 mL | 10 mM | 0.1980 mL | 0.9901 mL | 1.9802 mL |
*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℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 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: ≥ 0.5 mg/mL (0.99 mM); Clear solution
此方案可获得 ≥ 0.5 mg/mL (0.99 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 5.0 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-CDin saline) Solubility: ≥ 0.5 mg/mL (0.99 mM); Clear solution
此方案可获得 ≥ 0.5 mg/mL (0.99 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 5.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 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: ≥ 0.5 mg/mL (0.99 mM); Clear solution
此方案可获得 ≥ 0.5 mg/mL (0.99 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 5.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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