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Ixazomib citrate

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Chemical Structure| 1239908-20-3 同义名 : MLN9708;Ninlaro
CAS号 : 1239908-20-3
货号 : A183051
分子式 : C20H23BCl2N2O9
纯度 : 98%
分子量 : 517.12
MDL号 : MFCD29767859
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(483.45 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：
生物活性
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 Citrate is the citrate form of Ixazomib. 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.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.67mL

1.93mL

0.97mL

19.34mL

3.87mL

1.93mL
参考文献

[1]Chauhan D, Tian Z, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res. 2011 Aug 15;17(16):5311-21.

[2]Kupperman E, Lee EC, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010 Mar 1;70(5):1970-80.