423148-78-1
| 中文名称 | 423148-78-1 |
|---|---|
| 中文同义词 | 泛素激活酶E1抑制剂(PYZD-4409);化合物 T16699;化合物PYZD-4409;(E) -1-(3-氯-4-氟苯基)-4-((5-硝基呋喃-2-基)亚甲基)吡唑啉-3,5-二酮;PYZD 4409,泛素激活酶(E1)抑制剂 |
| 英文名称 | (E)-1-(3-chloro-4-fluorophenyl)-4-((5-nitrofuran-2-yl)Methylene)pyrazolidine-3,5-dione |
| 英文同义词 | (E)-1-(3-chloro-4-fluorophenyl)-4-((5-nitrofuran-2-yl)Methylene)pyrazolidine-3,5-dione;PYZD 4409;(E)-1-(3-chloro-4-fluorophenyl)-4-((5-nitrofuran-2-yl)Methylene)pyrazolidine-3,5-dione 3,5-Pyrazolidinedione, 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furanyl)methylene]-;PYZD4409;PYZD 4409;1-(3-Chloro-4-fluorophenyl)-4-[(5-nitro-2-furanyl)methylene]-3,5-pyrazolidinedione;3,5-Pyrazolidinedione, 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furanyl)methylene]-;PYZD-4409 >=98% (HPLC);Inhibitor,PYZD 4409,E3 ligating enzyme,E2 conjugating enzyme,PYZD-4409,inhibit,E1/E2/E3 Enzyme,Ubiquitin activating enzyme,E1 activating enzyme,Ubiquitin ligase,Ubiquitin conjugating enzyme,PYZD4409 |
| CAS号 | 423148-78-1 |
| 分子式 | C14H7ClFN3O5 |
| 分子量 | 351.67 |
| EINECS号 | |
| 相关类别 | 细胞生物学试剂 |
| Mol文件 | 423148-78-1.mol |
| 结构式 |  |
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 |
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. |
安全信息
| 更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
|---|---|---|---|---|---|
| 2024/01/25 | HY-13297 | PYZD-4409 | 1 mg | 1056元 | |
| 2024/01/25 | HY-13297 | 423148-78-1 PYZD-4409 | 423148-78-1 | 5mg | 2325元 |