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ML 120B dihydrochloride

Catalog No. T39199   CAS 1782573-78-7
Synonyms: ML120B dihydrochloride

MLN120B dihydrochloride (ML120B dihydrochloride) is a highly potent, orally active inhibitor of IKKβ. It competitively binds to ATP and exhibits an impressive IC50 value of 60 nM. This compound effectively suppresses the growth of multiple myeloma cells both in vitro and in vivo. Furthermore, MLN120B dihydrochloride is valuable in the field of rheumatoid arthritis research.

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ML 120B dihydrochloride Chemical Structure
ML 120B dihydrochloride, CAS 1782573-78-7
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Biological Description
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Description MLN120B dihydrochloride (ML120B dihydrochloride) is a highly potent, orally active inhibitor of IKKβ. It competitively binds to ATP and exhibits an impressive IC50 value of 60 nM. This compound effectively suppresses the growth of multiple myeloma cells both in vitro and in vivo. Furthermore, MLN120B dihydrochloride is valuable in the field of rheumatoid arthritis research.
In vitro 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 [ 3 H]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 IC 50 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]. Western Blot Analysis[1]Cell Line: MM.1S cells Concentration: 5 μM; 10 μM; 20 μM Incubation Time: 90 mintues Result: Inhibited p-IκB and p-P65 expression in a dose-dependent manner. Cell Viability Assay[1]Cell Line: Myeloma cell lines: MM.1S, MM.1R, RPMI 8226, RPMI-LR5, RPMI-Dox40, U266, and INA6 cells Concentration: 0-40 μM Incubation Time: 72 hours Result: Inhibited proliferation of multiple myeloma cell lines.
In vivo 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]. Animal Model: SCID mice implanted with human fetal bone chips and then INA6 cells are directly injected into mice[1]Dosage: 50 mg/kg Administration: Oral administration; twice daily; 3 weeks Result: Inhibited human multiple myeloma cell growth in vivo. Animal Model: Two-month-old female Lewis rats[2]Dosage: 30 mg/kg, 10 mg/kg, 3 mg/kg, or 1 mg/kg Administration: Oral administration; twice daily; 3 weeks Result: Protected against bone and cartilage destruction in a rat model.
Synonyms ML120B dihydrochloride
Molecular Weight 439.72
Formula C19H17Cl3N4O2
CAS No. 1782573-78-7

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

TargetMolReferences and Literature

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. 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. 3. Ansaldi D, et al. Imaging pulmonary NF-kappaB activation and therapeutic effects of MLN120B and TDZD-8. PLoS One. 2011;6(9):e25093. 4. 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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Keywords

ML 120B dihydrochloride 1782573-78-7 MLN120B dihydrochloride ML 120B Dihydrochloride ML120B Dihydrochloride ML120B dihydrochloride ML120B ML 120B MLN-120B dihydrochloride inhibitor inhibit

 

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