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].
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IC50& Target[1] |
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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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分子量 |
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性状 |
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Formula |
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CAS 号 |
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运输条件 |
Room temperature in continental US; may vary elsewhere.
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储存方式 |
Powder |
-20°C |
3 years |
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4°C |
2 years |
In solvent |
-80°C |
6 months |
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-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 |
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请根据半岛bd体育手机客户端 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半岛bd体育手机客户端 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
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1.
请依序添加每种溶剂: 10% DMSO40%PEG3005%Tween-8045% 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。
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2.
请依序添加每种溶剂: 10% DMSO90% (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。
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3.
请依序添加每种溶剂: 10% DMSO90%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。
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