431898-65-6

Basic information

• Product Name: N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE
• Synonyms: N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)pyridine-3-carboxamide;N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE;PS-1145 DIHYDROCHLORIDE;IKK Inhibitor X;PS 1145
• CAS NO: 431898-65-6
• Molecular Formula: C17H13Cl3N4O
• Molecular Weight: 395.67032
• Product Categories: A cell-permeable β-carboline compound that displays anti-inflammatory properties.
• Mol File: 431898-65-6.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 511.0±50.0 °C(Predicted)
• Appearance: yellow/
• Density: 1.513±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: >3mg/mL at ~60°C, clear (with warming for 2 minutes)
• PKA: 11.75±0.43(Predicted)
• CAS DataBase Reference: N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE(431898-65-6)
• EPA Substance Registry System: N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE(431898-65-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 431898-65-6(Hazardous Substances Data)

Usage

Description

N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE, also known as PS-1145 dihydrochloride, is a chemical compound that functions as an inhibitor of IκB kinase (IKK). It plays a crucial role in the cytokine-activated intracellular signaling pathway, which is essential for regulating the immune response. N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE also has the ability to inhibit osteoclast differentiation, making it a potential candidate for various therapeutic applications.

Uses

Used in Pharmaceutical Research:
N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE is used as a research tool for studying the role of IKK in various cellular processes and diseases. It helps researchers understand the underlying mechanisms of immune regulation and the potential therapeutic applications of targeting IKK.
Used in Cell Culture Studies:
In the culture medium, N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE is used as an IKK inhibitor for treating human epidermal keratinocytes (HEKs) and squamous carcinoma cells (SCCs). This application aids in investigating the role of IKK in the transcription of inflammatory mediators and the involvement of transcription factor p65 (RelA)/nuclear factor kappa-B (NF-κB) in various cellular processes.
Used in Immunology Research:
N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE is used as an IKK inhibitor to examine the involvement of NF-κB signaling in the cytotoxic effect of niclosamide on colorectal cancer (CRC) cells. This application helps researchers explore the potential of IKK inhibition in cancer therapy and the development of novel treatment strategies.
Used in Orthopedic Research:
As an inhibitor of osteoclast differentiation, N-(6-CHLORO-9H-PYRIDO[3,4-B]INDOL-8-YL)-3-PYRIDINECARBOXAMIDE DIHYDROCHLORIDE is used in orthopedic research to study the regulation of bone remodeling and the potential therapeutic applications in treating bone-related disorders, such as osteoporosis and bone metastasis.

Biological Activity

ps-1145 is an ikappab kinase (ikk) inhibitor.the iκb kinase is an enzyme complex involved in propagating the cellular response to inflammation. this enzyme complex is reported to be part of the upstream nf-κb signal transduction cascade.

Biochem/physiol Actions

PS-1145, a β-carboline derivative, blocks the phosphorylation and degradation of the inhibitor of nuclear factor kappa-β (NF-κB;). It also inhibits the subsequent activation of nuclear factor kappa-β (NF-κB) and thereby prevents the release of tumor necrosis factor-α (TNF-α) in lipopolysaccharide treated mice. PS-1145 hinders pro-inflammatory cytokine production and cell proliferation. It plays a potential therapeutic role in carcinogenesis in multiple myeloma. PS-1145 exhibits anti-tumor activity on nasopharyngeal carcinoma (NPC) cell lines.

in vitro

previous study found that ps-1145 could block tnfalpha-induced nf-kappab activation in a dose- and time-dependent manner in mm cells, which up-regulated ikappabalpha protein, enhanced blockade of nf-kappab activation. in addition, ps-1145 blocked the protective effect of il-6 against dex-induced apotosis and tnfalpha-induced icam-1 expression was also inhibited by ps-1145. moreover, ps-1145 inhibited both il-6 secretion from bmscs triggered by mm cell adhesion and proliferation of mm cells adherent to bmscs. however, ps-1145 could only partially inhibit mm cell proliferation. importantly, it was found that tnfalpha induced mm cell toxicity in the presence of ps-1145 [1]

in vivo

animal study showed that the intravenous application of ps-1145 could promote direct apoptosis in dmba-induced skin tumor in male wistar rats via blocking nf-κb and vegf activities [2].

IC 50

88 nm

references

[1] hideshima t,chauhan d,richardson p,mitsiades c,mitsiades n,hayashi t,munshi n,dang l,castro a,palombella v,adams j,anderson kc. nf-kappa b as a therapeutic target in multiple myeloma. j biol chem.2002 may 10;277(19):16639-47. [2] rajmani rs,gandham rk,gupta sk,et al. administration of iκb-kinase inhibitor ps1145 enhances apoptosis in dmba-induced tumor in male wistar rats. cell biol int.2015 nov;39(11):1317-28.