MLN2238

Research use only, not for human use.

A potent, selective, orally bioavailable proteasome inhibitor with IC50 of 3.4 nM.

A potent, selective, orally bioavailable proteasome inhibitor with IC50 of 3.4 nM; binds to and inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with Ki of 0.93 nM, weakly inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites (IC50 of 31 and 3,500 n M); inhibits growth and induces apoptosis in MM cells; shows improved antitumor activity in models of lymphoma compared with bortezomib.Blood Cancer Approved(In Vitro):Ixazomib (MLN2238) is an N-capped dipeptidyl leucine boronic acid and preferentially bound to and inhibited the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 value of 3.4 nM (Ki of 0.93 nM). At higher concentrations, Ixazomib (MLN2238) also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites (IC50 of 31 and 3,500 nM, respectively). Cell viability studies are performed in a variety of mammalian cell lines to compare the in vitro antiproliferative effects of Ixazomib (MLN2238) with Bortezomib. Studies performed with A375 (lung), H460 (lung), HCT-116 (colon), and HT-29 (colon) cells revealed similar LD50 values for the two compounds, which range from 4 to 58 nM. (In Vivo):Ixazomib (MLN2238) shows antitumor activity in the CWR22 xenograft model. The antitumor effects of Ixazomib (MLN2238) dosed at 14 mg/kg i.v. or 7 mg/kg i.v. are compared with Bortezomib dosed at 0.8 mg/kg i.v. or 0.4 mg/kg i.v. on a twice weekly regimen. The high dose for both Ixazomib (MLN2238) and Bortezomib shows similar antitumor activity in this model (T/C=0.36 and 0.44, respectively). However, Ixazomib (MLN2238) (7 mg/kg) shows greater efficacy at a 0.5 MTD dose compared with a 0.5 MTD dose of Bortezomib (0.4 mg/kg; T/C=0.49 compared with T/C=0.79, respectively) Ixazomib (MLN2238) shows time-dependent reversible proteasome inhibition; however, the proteasome dissociation half-life (t1/2) for Ixazomib (MLN2238) is determined to be 18 minutes.

——

——

Ixazomib | MLN 2238 | MLN-2238

Proteasome/Ubiquitin

Proteasome

20Sproteasome

Cancer

Blood cancer

1072833-77-2

361.0287

C14H19BCl2N2O4

>98% (HPLC)

DMSO: ≥ 28 mg/mL

CC(C)C[C@@H](B(O)O)NC(CNC(C1=CC(Cl)=CC=C1Cl)=O)=O

Boronic acid, B-[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-

(-20℃)

With Ice Pack

≥ 2 years