Ixazomib 含硼肽蛋白酶体抑制剂 (PI)，可抑制 20S 蛋白酶体的糜蛋白酶样蛋白水解 (β5) 位点，IC50为 3.4 nM，Ki为 0.93 nM。它还抑制半胱天冬酶样 (β1) 和胰蛋白酶样 (β2) 蛋白水解位点，IC50值为 31和3500 nM。

MLN2238, a second generation, boron-containing peptide proteasome inhibitor (PI), inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome (IC50/Ki: 3.4/0.93 nM, in cell-free assays), also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites (IC50: 31/3500 nM).

MLN2238对CWR22移植瘤具有抗癌活性.在WSU-DLCL2移植瘤模型中,MLN2238的肿瘤药效反应比bortezomib更强. 此外,在OCI-Ly10和PHTX22L模型中,MLN2238比 bortezomib具有更高的药效和抗癌活性.作用于移植瘤时,MLN2238的药效反应比bortezomib更较强,且其最大值更高,对肿瘤蛋白酶的抑制效果更持久.

MLN2238是MLN9708的生物活性代谢物。MLN2238和Bortezomib均为时间依赖性的蛋白酶体可逆抑制剂,但与Bortezomib(110分钟)相比,MLN2238（18分钟）作用于蛋白酶体的分离半衰期要快6倍。MLN2238的肿瘤药效 要高于Bortezomib。MLN2238是氮端加帽的二肽亮氨酸硼酸,对20S 蛋白酶体中糜蛋白酶类的水解位点有抑制作用（IC50/Ki：3.4/0.93 nM）。更高浓度时,MLN2238对20S蛋白酶体的caspase类水解位点（IC50：31 nM）和胰蛋白酶类水解位点（IC50：3.5 μM）也有抑制作用。MLN2238抑制Calu-6细胞（IC50：9.7 nM）。

Kinase assay : Calu-6 cells are cultured in MEM containing 10% fetal bovine serum and 1% penicillin/streptomycin and plated 1 day before the start of the experiment at 1 × 104 cells per well in a 384-well plate. Proteasome activity is assessed by monitoring hydrolysis of the chymotrypsin-like substrate Suc-LLVY-aminoluciferin in the presence of luciferase using the Proteasome-Glo assay reagents according to the manufacturer's instructions. Luminescence is measured using a LEADseeker instrument.

Calu-6 cells are cultured in MEM containing 10% FBS and 1% penicillin/streptomycin and plated 1 day before the start of the experiment at 1 × 104 cells per well in a 384-well plate. For IC50 determinations, cells are treated with varying concentrations of Bortezomib or MLN2238 in DMSO (0.5% final, v/v) for 1 hour at 37 °C. For reversibility experiments, cells are treated with either 1 μM Bortezomib or MLN2238 for 30 minutes at 37 °C and then washed thrice in medium to remove the Bortezomib or MLN2238. Cells are incubated for an additional 4 hours at 37 °C, after which the medium is removed and replaced with fresh medium. (Only for Reference)

1072833-77-2

C14H19BCl2N2O4

361.03

MLN2238;艾沙佐米

Ethanol:9 mg/mL (24.92 mM)
H2O:<1 mgml
DMSO:67 mg/mL (185.6 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years