| Identification | Back Directory | [Name]
MLN-120B | [CAS]
783348-36-7 | [Synonyms]
ML120B
MLN120B
MLN-120B
MLN 120B
ML120B; MLN 120B; MLN-120B
MLN120B;ML120B;MLN 120B;MLN-120B
N-(6-Chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methylnicotinamide
N-(6-Chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methyl-3-pyridinecarboxamide
3-Pyridinecarboxamide, N-(6-chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methyl- | [Molecular Formula]
C19H15ClN4O2 | [MDL Number]
MFCD17392835 | [MOL File]
783348-36-7.mol | [Molecular Weight]
366.8 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in H2O; ≥13.2 mg/mL in DMSO; ≥8.53 mg/mL in EtOH with gentle warming and ultrasonic | [form ]
solid | [color ]
Off-white to light yellow | [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]
Clc1cc2c([nH]c4c2ccnc4)c(c1OC)NC(=O)c3c(nccc3)C |
| Hazard Information | Back Directory | [Uses]
ML 120B is a novel competitive inhibitor of ATP and i-kappa-kinase-2 (IKK2), key regulator in the survival, proliferation and apoptosis resistance of lymphoma cells. | [Biological Activity]
mln120b is a potent and effective inhibitor of iκb kinase beta subunit (ikkβ) with ic50 value of 20 μm [1].ikk is an enzyme complex which is a part of the upstream of nf-κb signal transduction cascade. it is composed of three subunits, including ikkα, ikkβ and ikkγ. the ikkβ subunit is able to phosphorylate iκbα protein. normally, iκbα protein inactivate nf-κb transcription factors and keep them sequestering in inactive state in the cytoplasm. however, once iκbα protein is phosphorylated by ikkβ subunit, the iκbα protein will be dissociated from nf-κb transcription factor and thus remove the inactivation effect. therefore, the transcription of nf-κb will be activated. this signaling pathway is involved in many immune and inflammatory processes.in multiple myeloma cell line rpmi 8226 and ina 6, treatment of mln120b resulted in the dose-dependent inhibition of ikkβ-induced iκbα protein phosphorylation and subsequent nf-κb activation. additionally, it was observed that mln120b was able to block tnf-α-induced nf-κb activation in mm.1s cell line. these observations suggested the inhibitory action of mln120b on ikkβ. [1].in mouse model, polyarthritis was introduced in footpads, where ikkβ-induced nf-κb activation might result in a serial of advert effects. oral administration of mln120b (12 mg/kg twice daily) inhibited paw swelling in a dose-dependent manner, and offered protection against arthritis-induced weight loss. therefore, it could be implied that mln120b was able to inhibit ikkβ-induced nf-κb activation [2]. | [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; 1-30 mg/kg; twice daily; 3 weeks)?inhibits paw swelling in a dose-dependent manner and offers significant protection against arthritis-induced weight loss as well as cartilage and bone erosion. NF-κB activity in arthritic joints is also reduced after MLN120B administration[2]. | 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. |
| 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. |
| [target]
IkappaB beta | [IC 50]
IKKβ: 60 nM (IC50) | [References]
[1]. hideshima t, neri p, tassone p. mln120b, a novel ikappab kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. clin cancer res. 2006, 12(19): 5887-5894.
[2]. schopf l, savinainen a, anderson k. ikkbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis. arthritis rheum. 2006, 54(10): 3163-3173. |
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