783348-36-7

Basic information

• Product Name: MLN-120B
• Synonyms: N-(6-Chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methylnicotinamide;ML120B;MLN 120B;MLN120B;MLN-120B;N-(6-Chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methyl-3-pyridinecarboxamide
• CAS NO: 783348-36-7
• Molecular Formula: C19H15ClN4O2
• Molecular Weight: 366.801
• Product Categories: NF-kB
• Mol File: 783348-36-7.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Solubility: insoluble in H2O; ≥13.2 mg/mL in DMSO; ≥8.53 mg/mL in EtOH with gentle warming and ultrasonic
• CAS DataBase Reference: MLN-120B(CAS DataBase Reference)
• NIST Chemistry Reference: MLN-120B(783348-36-7)
• EPA Substance Registry System: MLN-120B(783348-36-7)

Safety Data

• Hazardous Substances Data: 783348-36-7(Hazardous Substances Data)

Usage

Description

MLN-120B is a novel competitive inhibitor of ATP and i-kappa-kinase-2 (IKK2), a key regulator in the survival, proliferation, and apoptosis resistance of lymphoma cells.

Uses

Used in Pharmaceutical Industry:
MLN-120B is used as an anticancer agent for its ability to inhibit the survival, proliferation, and apoptosis resistance of lymphoma cells. This makes it a promising candidate for the development of targeted therapies against lymphoma and potentially other cancer types.
Used in Cancer Research:
MLN-120B is used as a research tool for studying the role of IKK2 in cancer cell survival, proliferation, and apoptosis resistance. This helps researchers to better understand the molecular mechanisms underlying cancer development and progression, and to identify potential therapeutic targets for cancer treatment.
Used in Drug Development:
MLN-120B is used as a lead compound in the development of new drugs targeting IKK2 and related pathways. Its unique mechanism of action and potential efficacy against lymphoma cells make it a valuable asset in the search for novel cancer therapies.

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].

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.

Upstream product

• 65719-09-7 methyl 2-methylnicotinate 
• 1721-26-2 ethyl 2-methyl nicotinate 
• 431886-96-3 6-chloro-7-methoxy-9H-β-carbolin-8-ylamine 
• 3222-56-8 2-methylnicotinic acid 
• 361202-25-7 8-amino-6-chloro-β-carboline 

Relevant articles and documents

2-methyl nicotinate as well as preparation method and application thereof

The invention relates to 2-methyl nicotinate as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) reacting 1, 1, 3, 3-tetramethoxypropane or 1, 1, 3, 3-tetraethoxypropane under the action of acid to obtain a compound B; (2) reacting the compound B and beta-aminocrotonate in a first organic solvent to obtain 2-methyl nicotinate, wherein no foul acrolein is used in the process, the safety coefficient of production is effectively improved, the reaction raw materials are easy to obtain, the conditions are mild, the operation is simple, the yield is greater than 65%, the product purity reaches 98% or above, and the method is suitable for industrial production and has a wide application prospect. The obtained product can be used as an intermediate for synthesizing 2-methyl nicotinic acid, and can be used for synthesizing medicines.

BETA-CARBOLINES USEFUL FOR TREATING INFLAMMATORY DISEASE

This invention provides beta-carboline compounds of formula (I) wherein Ring A is a substituted pyridinyl, pyrimidinyl, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, pyranyl, tetrahydrofuranyl, cyclohexyl, cyclopentyl or thiomorpholinyl ring and R1, R2 and R3 are as described in the specification. The compounds are IKK-2 inhibitors that are useful for treating IKK-2 mediated diseases such as inflammatory diseases and cancer.