MLN120B

• CAT Number: I004879
• CAS Number: 783348-36-7
• Molecular Formula: C19H15ClN4O2
• Molecular Weight: 366.8
• Purity: ≥95%
• Target: IκB/IKK
• Solubility: DMSO: ≥ 31 mg/mL
• Storage: Store at -20°C
• IC50: MLN120B (20 umol/L) induced up to 35% and 75% inhibition, assessed by MTT assay and [3H]thymidine uptakein multiple myeloma cell lines, respectively.
• InChI: InChI=1S/C19H15ClN4O2/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)
• InChIKey: ZNOLRTPMNMPLHY-UHFFFAOYSA-N
• SMILES: O=C(C1=CC=CN=C1C)NC2=C(OC)C(Cl)=CC3=C2NC4=C3C=CN=C4

MLN120B is a potent and effective IKKbeta inhibitor.IC50 Value: MLN120B (20 umol/L) induced up to 35% and 75% inhibition, assessed by MTT assay and [3H]thymidine uptakein multiple myeloma cell lines, respectively.Target: IKKbetaNF-κB pathway blockers, such as MLN120B, are currently being explored for treatment of inflammatory diseases such as COPD and asthma[3].in vitro: MLN120B inhibits both baseline and tumor necrosis factor-α-induced nuclear factor-κB activation, associated with down-regulation of IκBα and p65 nuclear factor-κB phosphorylation. MLN120B triggers 25% to 90% growth inhibition in a dose-dependent fashion in multiple myeloma cell lines and significantly augments tumor necrosis factor-α-induced cytotoxicity in MM.1S cells. MLN120B augments growth inhibition triggered by doxorubicin and melphalan in both RPMI 8226 and IL-6-dependent INA6 cell lines. Neither IL-6 nor IGF-1 overcomes the growth-inhibitory effect of MLN120B. MLN120B inhibits constitutive IL-6 secretion by BMSCs by 70% to 80% without affecting viability. Importantly, MLN120B 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].in vivo: MLN120B MLN120B mediates anti-human multiple myeloma cell activity in vivo using a novel SCID-hu model, in which multiple myeloma cells grow in vivoin the context of the human bone marrow microenvironment. Eight SCID mice were implanted with human fetal bone chips (SCID-hu), into which human IL-6-dependent INA6 cells were directly injected. These mice were treated orally with either MLN120B (50 mg/kg) or vehicle control twice daily for 3 weeks[1]. Oral administration of ML120B inhibited paw swelling in a dose-dependent manner (median effective dosage 12 mg/kg twice daily) and offered significant protection against arthritis-induced weight loss as well as cartilage and bone erosion[2].Clinical trial: N/A

Reference

1:Imaging pulmonary NF-kappaB activation and therapeutic effects of MLN120B and TDZD-8. Ansaldi D, Hod EA, Stellari F, Kim JB, Lim E, Roskey M, Francis KP, Singh R, Zhang N.PLoS One. 2011;6(9):e25093. doi: 10.1371/journal.pone.0025093. Epub 2011 Sep 22. PMID: 21966423 Free PMC Article2:MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. Hideshima T, Neri P, Tassone P, Yasui H, Ishitsuka K, Raje N, Chauhan D, Podar K, Mitsiades C, Dang L, Munshi N, Richardson P, Schenkein D, Anderson KC.Clin Cancer Res. 2006 Oct 1;12(19):5887-94. PMID: 17020997 Free Article