423148-78-1
423148-78-1 性质
| 密度 | 1.662±0.06 g/cm3(Predicted) |
|---|---|
| 储存条件 | Store at -20°C |
| 溶解度 | 溶于二甲基亚砜 |
| 形态 | 固体 |
| 酸度系数(pKa) | 7.12±0.20(Predicted) |
| 颜色 | 棕色 |
423148-78-1 用途与合成方法
IC50: 20 μM (ubiquitin-activating enzyme UBA1)
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
LD
50
less than 10 μM in 5 of 8 leukemia and myeloma cell lines. In contrast, solid tumor cell lines were less sensitive with an
LD
50
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.
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 LD 50 less than 10 μM in 5 of 8 leukemia and myeloma cell lines. In contrast, solid tumor cell lines were less sensitive with an LD 50 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. |
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.
| 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. |
423148-78-1 价格(试剂级)
| 更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
|---|---|---|---|---|---|
| 2024-04-30 | HY-13297 | 1 mg | 750 | ||
| 2024-04-30 | HY-13297 | 423148-78-1 | 423148-78-1 | 5mg | 1800 |
