MLN120B dihydrochloride

• CAT Number: R061469
• CAS Number: 1782573-78-7
• Molecular Formula: C19H17Cl3N4O2
• Molecular Weight: 439.72
• Purity: ≥95%
• Synonyms: N-(6-chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methylpyridine-3-carboxamide;dihydrochloride
• InChI: InChI=1S/C19H15ClN4O2.2ClH/c1-10-11(4-3-6-22-10)19(25)24-17-16-13(8-14(20)18(17)26-2)12-5-7-21-9-15(12)23-16;;/h3-9,23H,1-2H3,(H,24,25);2*1H
• InChIKey: AWKOVWFBTRXQLW-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC=N1)C(=O)NC2=C3C(=CC(=C2OC)Cl)C4=C(N3)C=NC=C4.Cl.Cl

MLN120B dihydrochloride (ML120B dihydrochloride) is a potent, ATP competitive, and orally active inhibitor of IKKβ with an IC50 of 60 nM. MLN120B inhibits multiple myeloma cell growth in vitro and in vivo and also can be used for the research of rheumatoid arthritis[1][2].
MLB120B (0-20 μM; 90 minutes) inhibits phosphorylation and degradation of IκB in RPMI 8226 and INA6 cells; however, no significant inhibition is observed in MM.1S cells[1].MLB120B (1.25-20 μM; 90 minutes) completely abrogates TNF-a-induced phosphorylation and degradation of IκB in a dosedependent fashion. Phosphorylation of p65 NF-κB induced by TNF-a is also blocked by MLN120B[1].MLN120B inhibits proliferation of multiple myeloma cell lines. MM.1S, MM.1R, RPMI 8226, RPMI-LR5, RPMI-Dox40, U266, and INA6 cells. Five percent to fifty percent and 18% to 70% inhibition in proliferation is observed at doses >20 uM and [3H]thymidine uptake, respectively[1].MLN120B (1.25-40 μM; 72 hours) almost completely blocks stimulation of MM.1S, U266, and INA6 cell growth, as well as IL-6 secretion from BMSCs, induced by multiple myeloma cell adherence to BMSCs[1].MLN120B shows an inhibitory effect on LPS induced NF-κB activation in RAW267.4 cells. The IC50 values of MLN120B is 1.4 µM, 14.8 µM or 27.3 µM for NF-κB2-luc2, IL8-luc2 or TNF-AIP3-luc2 reporter transfected cells, respectively[3].
MLN120B (oral administration; 50 mg/kg; twice daily; 3 weeks) induces a reduction of shuIL-6R, marker of tumor growth, marker of tumor growth. It also leads to a rend toward prolonged survival in animals treated versus control[1].MLN120B (oral administration; 50 mg/kg; twice daily; 3 weeks) induces a reduction of shuIL-6R, marker of tumor growth, marker of tumor growth. It also leads to a rend toward prolonged survival in animals treated versus control[3].

Reference

[1]. Hideshima T, et all. MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. Clin Cancer Res. 2006 Oct 1;12(19):5887-94.
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[2]. Schopf L, et al. IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis. Arthritis Rheum. 2006 Oct;54(10):3163-73.
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[3]. Ansaldi D, et al. Imaging pulmonary NF-kappaB activation and therapeutic effects of MLN120B and TDZD-8. PLoS One. 2011;6(9):e25093.
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[4]. [3].Nagashima K, et al. Rapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical inhibitor of IKKbeta. Blood. 2006 Jun 1;107(11):4266-73.
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