423148-78-1
423148-78-1 結(jié)構(gòu)式
基本信息
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
(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]-
物理化學(xué)性質(zhì)
常見問題列表
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. |