Synthesis and biological evaluation of N-cyclopropylbenzamide-benzophenone hybrids as novel and selective p38 mitogen activated protein kinase (MAPK) inhibitors

Heo, Jun; Shin, Han-Bo; Lee, Jun; Kim, Tae-Lim; Inn, Kyung‐Soo; Kim, Nam‐Jung

doi:10.1016/j.bmcl.2015.06.036

Cited by 22 publications

(16 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, these results suggested that NJK-14047 might be a potential candidate for further evaluation as an antiviral agent against HBV and other viruses by suppressing viral replication and infection-mediated inflammatory responses (20).…”

Section: Discussionmentioning

confidence: 82%

“…Despite extensive efforts to develop specific p38 MAPK inhibitors, no therapeutically approved p38 MAPK inhibitors have been established. In an effort to develop novel p38 MAPK-inhibiting chemical agents, we have reported on several novel biphenyl amides and showed that some of them specifically inhibit p38 MAPK activity (20).…”

Section: Discussionmentioning

confidence: 99%

“…1). Twelve biphenyl amides were efficiently synthesized, as previously reported by our group and other researchers (19,20), and tested for their abilities to suppress in vitro p38 MAPK enzyme activity using the SelectScreen kinase-profiling service (Life Technologies). Inhibition of p38 MAPK with 1 M biphenyl amide compound ranged from 6% to 97% ( Fig.…”

Section: Synthesis and Evaluation Of P38 Mapk-inhibitory Activities Omentioning

confidence: 99%

“…In our previous study, NJK14047 was found to show dose-dependent inhibitory effects on p38 MAPK (IC 50 ϭ 27 nM) (20). To confirm p38 MAPK inhibition in hepatocytes, HepG2 cells transfected with a plasmid containing the HBV genome (pHBV-1.2x; GenBank accession no.…”

Section: Synthesis and Evaluation Of P38 Mapk-inhibitory Activities Omentioning

confidence: 99%

“…Within the past decade, several biphenyl amides have been developed as novel p38 MAPK inhibitors (19). In particular, we recently reported a class of novel biphenyl amide p38 MAPK inhibitors containing a benzophenone moiety and demonstrated that some of these inhibitors have potent p38 MAPK-inhibitory activities and kinase selectivities (14,20). In the current study, we explored the antiviral activities of these p38 MAPK inhibitors against HBV.…”

mentioning

confidence: 99%

See 4 more Smart Citations

An Effective Antiviral Approach Targeting Hepatitis B Virus with NJK14047, a Novel and Selective Biphenyl Amide p38 Mitogen-Activated Protein Kinase Inhibitor

Kim

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Despite recent advances in therapeutic strategies against hepatitis B virus (HBV) infection, chronic hepatitis B remains a major global health burden. Recent studies have shown that targeting host factors instead of viral factors can be an effective antiviral strategy with low risk of the development of resistance. Efforts to identify host factors affecting viral replication have identified p38 mitogen-activated protein kinase (MAPK) as a possible target for antiviral strategies against various viruses, including HBV. Here, a series of biphenyl amides were synthesized as novel p38 MAPK selective inhibitors and assessed for their anti-HBV activities. The suppression of HBV surface antigen (HBsAg) production by these compounds was positively correlated with p38 MAPK-inhibitory activity. The selected compound NJK14047 displayed significant anti-HBV activity, as determined by HBsAg production, HBeAg secretion, and HBV production. NJK14047 efficiently suppressed the secretion of HBV antigens and HBV particles from HBV genome-transfected cells and HBV-infected sodium taurocholate cotransporting polypeptide-expressing human hepatoma cells. Furthermore, NJK14047 treatment resulted in a significant decrease of pregenomic RNA and covalently closed circular DNA (cccDNA) of HBV in HBV-harboring cells, indicating its ability to inhibit HBV replication. Considering that suppression of HBsAg secretion and elimination of cccDNA of HBV are the major aims of anti-HBV therapeutic strategies, the results suggested the potential use of these compounds as a novel class of anti-HBV agents targeting host factors critical for viral infection.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Synthesis and Evaluation Of P38 Mapk-inhibitory Activities Omentioning

confidence: 99%

Section: Synthesis and Evaluation Of P38 Mapk-inhibitory Activities Omentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations