423148-78-1
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- CAS号:
- 423148-78-1
- 英文名:
- (E)-1-(3-chloro-4-fluorophenyl)-4-((5-nitrofuran-2-yl)Methylene)pyrazolidine-3,5-dione
- 英文别名:
- PYZD 4409;PYZD4409;PYZD 4409;PYZD-4409 >=98% (HPLC);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]-;(E)-1-(3-chloro-4-fluorophenyl)-4-((5-nitrofuran-2-yl)Methylene)pyrazolidine-3,5-dione;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;(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]-
- 中文名:
- 423148-78-1
- 中文别名:
- 化合物 T16699;化合物PYZD-4409;泛素激活酶E1抑制剂(PYZD-4409);PYZD 4409,泛素激活酶(E1)抑制剂;(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
- CBNumber:
- CB82609290
- 分子式:
- C14H7ClFN3O5
- 分子量:
- 351.67
- MOL File:
- 423148-78-1.mol
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423148-78-1化学性质
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密度:
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1.662±0.06 g/cm3(Predicted)
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储存条件:
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Store at -20°C
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溶解度:
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Soluble in DMSO
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形态:
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solid
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酸度系数(pKa):
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7.12±0.20(Predicted)
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颜色:
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Brown
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423148-78-1性质、用途与生产工艺
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。
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
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Cell Line:
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Myeloma, leukemia, and solid tumor cell lines, primary AML cells and normal hematopoietic cells
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Concentration:
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10 μM, 20 μM, 30 μM, 40 μM
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Incubation Time:
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72 hours
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Result:
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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.
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Western Blot Analysis
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Cell Line:
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K562 leukemia cells
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Concentration:
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50 μM
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Incubation Time:
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4 hours
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Result:
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Blocked the E1-dependent conjugation of ubiquitin to the E2 enzyme cdc34.
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RT-PCR
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Cell Line:
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K562 cells
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Concentration:
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0 μM, 10 μM, 25 μM
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Incubation Time:
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24 hours
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Result:
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Significantly increased both mRNA and protein levels of Grp78 and Hsp70.
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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.
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Animal Model:
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Male severe combined immunodeficient (SCID) mice with MDAY-D2 murine leukemia cells
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Dosage:
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10 mg/kg
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Administration:
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Intraperitoneal injection; daily on alternate days; for 16 days
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Result:
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Delayed tumor growth and decreased tumor weight without untoward toxicity.
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423148-78-1
上下游产品信息
上游原料
下游产品
| 更新日期 | 产品编号 | 产品名称 | CAS编号 | 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 |
423148-78-1, 423148-78-1 相关搜索:
- 酶
- 化学试剂
- 细胞生物学试剂
- C14H7ClFN3O5
- PYZD 4409,泛素激活酶(E1)抑制剂
- (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
- 化合物PYZD-4409
- 化合物 T16699
- 泛素激活酶E1抑制剂(PYZD-4409)
- 423148-78-1
- 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
- PYZD-4409 >=98% (HPLC)
- 3,5-Pyrazolidinedione, 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furanyl)methylene]-
- 1-(3-Chloro-4-fluorophenyl)-4-[(5-nitro-2-furanyl)methylene]-3,5-pyrazolidinedione
- PYZD4409;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]-
- PYZD 4409
- (E)-1-(3-chloro-4-fluorophenyl)-4-((5-nitrofuran-2-yl)Methylene)pyrazolidine-3,5-dione