PYZD-4409|cas:423148-78-1|西域试剂

PYZD-4409,98.0%

产品编号：Bellancom-13297| CAS NO：423148-78-1| 分子式：C₁₄H₇ClFN₃O₅| 分子量：351.67

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-13297	￥2325.00	杭州北京（现货）
Bellancom-13297	￥3534.00	杭州北京（现货）
Bellancom-13297	￥8370.00	杭州北京（现货）
Bellancom-13297	￥13020.00	杭州北京（现货）

增值税发票√顺丰快递√订货电话：18601927057

PYZD-4409

产品介绍

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。

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.

体外研究

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.
PYZD-4409 (50 μM; 4 hours; K562 leukemia cells) treatment blocks the E1-dependent conjugation of ubiquitin to the E2 enzyme cdc34.
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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay

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

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

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.

西域 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
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.

体内研究

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.

西域 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
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.

体内研究

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.

西域 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
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.

性状

Solid

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