PYZD-4409

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PYZD-4409  纯度: ≥98.0%

PYZD-4409 是 ubiquitin-activating enzyme UBA1 的特异性抑制剂，其 IC50 值为 20 μM。PYZD-4409 能诱导恶性细胞死亡，并优先抑制原发性急性髓性白血病细胞的生长。

PYZD-4409

PYZD-4409 Chemical Structure

CAS No. : 423148-78-1

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ￥2558 In-stock
5 mg ￥2325 In-stock
10 mg ￥3534 In-stock
50 mg ￥8370 In-stock
100 mg ￥13020 In-stock
200 mg   询价  
500 mg   询价  

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PYZD-4409 相关产品

•相关化合物库:

  • Bioactive Compound Library Plus
  • Metabolism/Protease Compound Library
  • Anti-Cancer Compound Library
  • Oxygen Sensing Compound Library
  • Ubiquitination Compound Library
  • Endoplasmic Reticulum Stress Compound Library
  • Anti-Blood Cancer Compound Library
  • Anti-Liver Cancer Compound Library

生物活性

PYZD-4409 is a specific inhibitor of the ubiquitin-activating enzyme UBA1 with an IC50 of 20 μM (cell-free enzymatic assay). PYZD-4409 induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells[1].

IC50 & Target

IC50: 20 μM (ubiquitin-activating enzyme UBA1)[1]
体外研究
(In Vitro)

PYZD-4409 (10-40 μM; 72 hours; myeloma, leukemia, and solid tumor cell lines, primary AML cells and normal hematopoietic cells) induces cell death with a LD50 less than 10 μM in 5 of 8 leukemia and myeloma cell lines. In contrast, solid tumor cell lines were less sensitive with an LD50 of approximately 15 to 20 μM. PYZD-4409 is preferentially cytotoxic to malignant cells over normal hematopoietic cells[1].
PYZD-4409 (50 μM; 4 hours; K562 leukemia cells) treatment blocks the E1-dependent conjugation of ubiquitin to the E2 enzyme cdc34[1].
PYZD-4409 (0-25 μM; 24 hours; K562 leukemia cells) significantly increases both mRNA and protein levels of Grp78 and Hsp70. In addition, PYZD-4409 increases levels of phospho-JNK and phospho-p38 mitogen-activated protein kinase, which have also been linked to ER stress and the unfolded protein response[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay[1]

Cell Line: Myeloma, leukemia, and solid tumor cell lines, primary AML cells and normal hematopoietic cells
Concentration: 10 μM, 20 μM, 30 μM, 40 μM
Incubation Time: 72 hours
Result: Induced cell death with a LD50 less than 10 μM in 5 of 8 leukemia and myeloma cell lines. In contrast, solid tumor cell lines were less sensitive with an LD50 of approximately 15 to 20 μM.

Western Blot Analysis[1]

Cell Line: K562 leukemia cells
Concentration: 50 μM
Incubation Time: 4 hours
Result: Blocked the E1-dependent conjugation of ubiquitin to the E2 enzyme cdc34.

RT-PCR[1]

Cell Line: K562 cells
Concentration: 0 μM, 10 μM, 25 μM
Incubation Time: 24 hours
Result: Significantly increased both mRNA and protein levels of Grp78 and Hsp70.

体内研究
(In Vivo)

PYZD-4409 (10 mg/kg; intraperitoneal injection; daily on alternate days; for 16 days; male severe combined immunodeficient mice) decreases tumor weight and volume without untoward toxicity[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male severe combined immunodeficient (SCID) mice with MDAY-D2 murine leukemia cells[1]
Dosage: 10 mg/kg
Administration: Intraperitoneal injection; daily on alternate days; for 16 days
Result: Delayed tumor growth and decreased tumor weight without untoward toxicity.

分子量

351.67

Formula

C14H7ClFN3O5
CAS 号

423148-78-1
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
溶解性数据
In Vitro: 

DMSO : ≥ 35 mg/mL (99.53 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.8436 mL 14.2179 mL 28.4357 mL
5 mM 0.5687 mL 2.8436 mL 5.6872 mL
10 mM 0.2844 mL 1.4218 mL 2.8436 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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 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: ≥ 2.5 mg/mL (7.11 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (7.11 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 25.0 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。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Xu GW, et al. The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. Blood. 2010 Mar 18;115(11):2251-9.

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