MLN2238 is a potent proteasome inhibitor (PI) with potential antineoplastic activity. MNL2238 is also .the biologically active form of MLN9708. MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMyc(Cα)/Bcl-X(L) GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model.
Chemical Formula: C14H19BCl2N2O4
Exact Mass: 360.08149
Molecular Weight: 361.02866
Elemental Analysis: C, 46.58; H, 5.30; B, 2.99; Cl, 19.64; N, 7.76; O, 17.73
MLN-9708 FREE BASE
Boronic acid, b-((1R)-1-((2-((2,5-dichlorobenzoyl)amino)acetyl)amino)-3-methylbutyl)-
Chemical Name: (R)-(1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)boronic acid
InChi Code: InChI=1S/C14H19BCl2N2O4/c1-8(2)5-12(15(22)23)19-13(20)7-18-14(21)10-6-9(16)3-4-11(10)17/h3-4,6,8,12,22-23H,5,7H2,1-2H3,(H,18,21)(H,19,20)/t12-/m0/s1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
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, 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 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.
MLN2238 shows antitumor activity in the CWR22 xenograft model. The antitumor effects of (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 MLN2238 and Bortezomib shows similar antitumor activity in this model (T/C=0.36 and 0.44, respectively). However, 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) MLN2238 shows time-dependent reversible proteasome inhibition; however, the proteasome dissociation half-life (t1/2) for MLN2238 is determined to be 18 minutes.
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