[CAS NO. 1072833-77-2] Ixazomib (MLN2238)

Name: Ixazomib (MLN2238)
Brand: Arctom Scientific
SKU: SLK-S2180

Ships within

Stock

Price

Qty

Total

$0.00

Please click "REQUEST A QUOTE" button if you need other sizes or custom synthesis

request a quote

If there is no stock, or you need other sizes or custom synthesis, please:

PRODUCTS SPECIFICATIONS [1072833-77-2]

Store

Catalog

SLK-S2180

Brand

Selleck

CAS

1072833-77-2

DESCRIPTION [1072833-77-2]

Overview

MDL	-
Molecular Weight	361.03
Molecular Formula	C14H19BCl2N2O4
SMILES	C(NCC(N[C@@H](CC(C)C)B(O)O)=O)(=O)C1=C(Cl)C=CC(Cl)=C1

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Description

Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the with and of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Ixazomib (MLN2238) induces . Phase 3.

Features

A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.

Targets

20S proteasome ^[1] (Cell-free assay)	20S proteasome ^[1] (Cell-free assay)
0.93 nM(Ki)	3.4 nM

In vitro

At higher concentrations, MLN2238 also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites with IC50 of 31nM and 3.5uM, respectively. MLN2238 inhibits Calu-6 cell with IC50 of 9.7 nM. MLN2238 is a selective, potent, and reversible inhibitor of the proteasome in tumor cells. MLN2238 shows time-dependent reversible proteasome inhibition. Both MLN2238 and Bortezomib shows time-dependent reversible proteasome inhibition; however, the proteasome dissociation half-life for MLN2238 is determined to be ∼6-fold faster than that of Bortezomib (18 and 110 minutes, respectively). MLN2238 dissociates more rapidly from the proteasome than Bortezomib, consistent with faster recovery of proteasome activity observed in the Proteasome-Glo assay. MLN2238 has a greater overall tumor pharmacodynamic effect than Bortezomib as assessed by 20S inhibition. MLN2238 is the biologically active form of MLN9708.

In vivo

MLN2238 induces a greater pharmacodynamic response than Bortezomib in xenograft tumors. MLN2238 shows greater maximum and sustained tumor proteasome inhibition compared with Bortezomib in xenograft models. These results confirm that the improved tumor exposure seen with MLN2238 translates into an improved tumor pharmacodynamic response both at the level of and downstream from the proteasome. MLN2238 shows antitumor activity in the CWR22 xenograft model. MLN2238 shows greater tumor pharmacodynamic responses in WSU-DLCL2 xenografts compared with Bortezomib. Similarly, Bortezomib treatment only led to a minor increase in GADD34 levels in WSU-DLCL2 xenograft tumors, whereas MLN2238 strongly induces its expression. MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with Bortezomib in both OCI-Ly10 and PHTX22L models.

References

[1] Kupperman E, et al. Cancer Res, 2010, 70(5), 1970-80
[2] Lee EC, et al. Clin Cancer Res, 2011, 17(23), 7313-23.

Synonyms

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

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

MLN 2238

Ixazomib

Ninlaro

(R)-1-(2-(2,5-Dichlorobenzamido)acetamido)-3-methylbutylboronicacid