产品说明书
Ixazomib
 |
同义名 : | 伊沙佐米(MLN2238) ;MLN2238 |
| CAS号 : | 1072833-77-2 | |
| 货号 : | A172813 | |
| 分子式 : | C14H19BCl2N2O4 | |
| 纯度 : | 99%+ | |
| 分子量 : | 361.029 | |
| MDL号 : | MFCD18251438 | |
| 存储条件： |
粉末 Inert atmosphere,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月 |
|
| 溶解度 : |
DMSO: 60 mg/mL(166.19 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
|
| 动物实验配方： |
5% DMSO+45% PEG 300+water 17 mg/mL |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
|
||
| 描述 | The ubiquitin-proteasome system is responsible for the regulation of cellular protein homeostasis. By inhibiting proteasome activity, the anti-proliferative signals and the apoptotic pathways can be activated in cells, which makes proteasome an attractive therapeutic target in cancer treatment. Ixazomib is an N-capped dipeptidyl leucine boronic acid that inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 value of 3.4 nmol/l (Ki value of 0.93 nmol/l). It also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 values of 31 and 3500 nmol/l, respectively. The proteasome dissociation half-life (t1/2) for ixazomib is 18 minutes. In MDA-MB-231 cells expressing a 4 Ub-Luc reporter, ixazomib inhibited proteasome activity with an EC50 value of 525 nmol/l. In HEK293 cells stably expressing a NF-κB-Luc reporter, ixazomib inhibited TNF-α-induced activation of NF-κB pathway with an EC50 value of 55 nmol/l. The anti-proliferative effects of ixazomib in A375 (lung), H460 (lung), HCT-116 (colon), and HT-29 (colon) cells were determined by cell viability assay with LD50 values ranged from 19 – 58 nmol/l. In mice i.v. administrated with a single dose of ixazomib at 14 mg/kg, the blood volume distribution at steady state was 20.2 L/kg. In Sprague-Dawley rats i.v. injected with a single of ixazomib at 0.2 or 0.3 mg/kg, the plasma exposure (AUC0-48h) of ixazomib was 704 and 1070 h.ng/ml, respectively. In CB17-SCID mice bearing xenograft tumors, the maximum level of blood proteasome inhibition was 83.1% following an acute i.v. treatment of 14 mg/kg ixazomib. The tumor to blood AUE ratio for ixazomib in human prostate tumor (CWR22) and human lymphoma tumor (WSU-DLCL2s) xenografts was 1.56 and 2.03, respectively. Ixazomib dosed at 7 mg/kg or 14 mg/kg showed significant antitumor effects in xenografts 22 days after the administration. | ||
| 作用机制 | Ixazomib inhibits 20S proteasome by binding to the chymotrypsin-like proteolytic (β5) site of the proteasome. | ||
| 临床研究 | |||||
|---|---|---|---|---|---|
| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
| NCT02765854 | Recurrent Plasma Cell Myeloma ... 展开 >> Refractory Plasma Cell Myeloma 收起 << | Phase 2 | Recruiting | September 2020 | United States, Georgia ... 展开 >> Grady Memorial Hospital Recruiting Atlanta, Georgia, United States, 30303 Contact: Stephanie McMillan, RN, MSN 404-778-1361 sjmcmil@emory.edu Emory University/Winship Cancer Institute Recruiting Atlanta, Georgia, United States, 30322 Contact: Jennifer Shipp 404-778-4191 jennifer.shipp@emory.edu United States, Michigan University of Michigan/Rogel Cancer Center Recruiting Ann Arbor, Michigan, United States, 48109 Contact: Craig Cole, MD colec@med.umich.edu United States, Missouri Washington University/Siteman Cancer Center Recruiting Saint Louis, Missouri, United States, 63110 Contact: Ravi Vij, MD rvij@wustl.edu 收起 << |
| NCT02400437 | Waldenstrom's Macroglobulinemi... 展开 >>a 收起 << | Phase 2 | Active, not recruiting | September 2021 | United States, Massachusetts ... 展开 >> Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 收起 << |
| NCT02158975 | Lymphoma, T-Cell | Phase 2 | Completed | - | United States, Michigan ... 展开 >> University of Michigan Hospital Ann Arbor, Michigan, United States, 48109 收起 << |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
|
1 mM 5 mM 10 mM |
2.77mL 0.55mL 0.28mL |
13.85mL 2.77mL 1.38mL |
27.70mL 5.54mL 2.77mL |
| 参考文献 |
|---|