MLN2238

Cas：1072833-77-2 (free)

Product Information：

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

Synonym: 

Ixazomib

1072833-77-2

MLN2238

MLN-2238

MLN 2238

(R)-1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutylboronic acid

(R)-(1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)boronic acid

UNII-71050168A2

CHEMBL2141296

71050168A2

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

Ixazomib [INN]

Ixazomib [USAN:INN]

Ixazomib (MLN2238)

Ixozamib

Ixazomib Impurity

Ixazomib-d3

Ixazomib (USAN)

Ixazomib(MLN2238)

MLN2238(Ixazomib)

Ixazomib (MLN-2238)

cc-437

C14H19BCl2N2O4

GTPL8450

MLN-9708 FREE BASE

SCHEMBL3742758

CHEBI:90942

CTK4A5116

KS-00000PQX

EX-A547

BCP02410

BCP24078

ABP000732

BDBM50398609

s2180

AKOS015995120

ZINC169946773

BCP9000953

CCG-264938

CS-1657

DB09570

SB19501

Boronic acid, b-((1R)-1-((2-((2,5-dichlorobenzoyl)amino)acetyl)amino)-3-methylbutyl)-

1072833-77-2 (free)

NCGC00249611-01

NCGC00249611-03

NCGC00249611-04

AC-28456

AS-55976

AT-42310

HY-10453

SC-94531

AB0033791

SW219743-1

X7547

J3.602.191H

D10130

MLN2238,MLN 2238,MLN-2238/

S-7673

J-001749

BRD-K78659596-001-01-3

Q20948663

1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutylboronic acid

N-[(1R)-1-borono-3-methylbutyl]-N(2)-(2,5-dichlorobenzoyl)glycinamide

[(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methyl-butyl]boronic acid

[(1R)-1-{2-[(2,5-dichlorophenyl)formamido]acetamido}-3-methylbutyl]boronic acid

MLN-2238|||[(1R)-1-[[2-[(2,5-Dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boron

Chemical Name: (R)-(1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)boronic acid

InChi Key:

MXAYKZJJDUDWDS-LBPRGKRZSA-N

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

Smiles Code:

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

Technical Data：

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

In Vitro：

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.

In Vivo：

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.

References：

1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548002/ PubMed PMID: 31643334.

2. Tzogani K, Florez B, Markey G, Caleno M, Olimpieri OM, Melchiorri D, Hovgaard DJ, Sarac SB, Penttilä K, Lapvetelainen T, Salmonson T, Bergh J, Gisselbrecht C, Pignatti F. European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. ESMO Open. 2019 Sep 8;4(5):e000570. doi: 10.1136/esmoopen-2019-000570. eCollection 2019. Review. PubMed PMID: 31555488; PubMed Central PMCID: PMC6735670.

3. Armoiry X, Spath HM, Clarke A, Connock M, Sutcliffe P, Dussart C. Comparison of health technology assessment for new medicines in France and England: an example based on ixazomib for patients with relapsed or refractory multiple myeloma. J Mark Access Health Policy. 2019 Jul 30;7(1):1648971. doi: 10.1080/20016689.2019.1648971. eCollection 2019. Review. PubMed PMID: 31489149; PubMed Central PMCID: PMC6711145.

4. Smolewski P, Rydygier D. Ixazomib: an investigational drug for the treatment of lymphoproliferative disorders. Expert Opin Investig Drugs. 2019 May;28(5):421-433. doi: 10.1080/13543784.2019.1596258. Epub 2019 Apr 13. Review. PubMed PMID: 30907163.

5. Richardson PG, Zweegman S, O'Donnell EK, Laubach JP, Raje N, Voorhees P, Ferrari RH, Skacel T, Kumar SK, Lonial S. Ixazomib for the treatment of multiple myeloma. Expert Opin Pharmacother. 2018 Dec;19(17):1949-1968. doi: 10.1080/14656566.2018.1528229. Epub 2018 Nov 13. Review. PubMed PMID: 30422008.

Products are for research use only. Not for human use