423148-78-1
| 中文名稱 | 423148-78-1 |
|---|---|
| 中文同義詞 | 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)亞甲基)吡唑啉-3,5-二酮;PYZD 4409,泛素激活酶(E1)抑制劑;化合物PYZD-4409,10 MM DMSO 溶液;泛素激活酶E1抑制劑(PYZD-4409);PYZD-4409 (PYZD4409;PYZD 4409) |
| 英文名稱 | (E)-1-(3-chloro-4-fluorophenyl)-4-((5-nitrofuran-2-yl)Methylene)pyrazolidine-3,5-dione |
| 英文同義詞 | (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號 | 423148-78-1 |
| 分子式 | C14H7ClFN3O5 |
| 分子量 | 351.67 |
| EINECS號 | |
| 相關(guān)類別 | 細(xì)胞生物學(xué)試劑 |
| Mol文件 | 423148-78-1.mol |
| 結(jié)構(gòu)式 |  |
423148-78-1 性質(zhì)
| 密度 | 1.662±0.06 g/cm3(Predicted) |
|---|---|
| 儲存條件 | Store at -20°C |
| 溶解度 | 溶于二甲基亞砜 |
| 形態(tài) | 固體 |
| 酸度系數(shù)(pKa) | 7.12±0.20(Predicted) |
| 顏色 | 棕色 |
| InChI | 1S/C14H7ClFN3O5/c15-10-5-7(1-3-11(10)16)18-14(21)9(13(20)17-18)6-8-2-4-12(24-8)19(22)23/h1-6H,(H,17,20) |
| InChIKey | MSYMKEYWUWVZQY-UHFFFAOYSA-N |
| SMILES | FC1=CC=C(N2C(C(C(N2)=O)=CC3=CC=C([N+]([O-])=O)O3)=O)C=C1Cl |
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
| WGK Germany | WGK 3 |
|---|---|
| 存儲類別 | 6.1C - 可燃，急性毒性 類別3 毒性化合物或者引起慢性影響的化合物 |
| 危險性類別 | 急性毒性 類別3經(jīng)口 眼部刺激 類別2 經(jīng)皮刺激 類別2 特異性靶器官毒性-一次接觸，類別3 |
| 更新日期 | 產(chǎn)品編號 | 產(chǎn)品名稱 | CAS號 | 包裝 | 價格 |
|---|---|---|---|---|---|
| 2026/06/05 | HY-13297 | PYZD-4409 | 423148-78-1 | 1 mg | 750元 |
| 2026/06/05 | HY-13297 | 423148-78-1 PYZD-4409 | 423148-78-1 | 5mg | 1800元 |