Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease

Zhang, Jing; Romero, Jan Antoinette C.; Chan, Ariane; Goss, Jennifer; Stucka, Sabrina; Cross, Jason B.; Chamberlain, Brian T.; Varoglu, Mustafa; Chandonnet, Haoqun; Ryan, D. M.; Lippa, Blaise

doi:10.1016/j.bmcl.2015.06.046

Cited by 15 publications

(18 citation statements)

References 14 publications

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“…Similar results have also been showed that CCR9 was significantly up-regulated in all tested tissues except in the spleen of miiuy croaker after challenging with Vibrio anguillarum (Zhu et al 2013). CCR9 was a key chemokine receptor mediating the local inflammatory responses in the gastrointestinal tract (Zhang et al 2015). In a previous study, the expression of CCR9 transcripts in the gut mucosal tissue of sea bass was increased after treated with the recombinant TNF-α alongside an oral vaccine against V. anguillarum (Galindo-Villegas et al 2013).…”

Section: Tissue Distribution Of the Rcccr9supporting

confidence: 82%

Molecular characterization and expression analysis of the CCR9 gene from cobia (Rachycentron canadum) following bacterial and poly I:C challenge

Deng

Cheng

et al. 2019

Journal of Applied Animal Research

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Chemokine receptors play an important role in coordination of cell trafficking in many biological processes. In this study, a CC chemokine receptor 9 of cobia Rachycentron canadum (RcCCR9) was identified. Analysis of the ORF (1119 bp) of RcCCR9 revealed a predicted protein of 41.87 kDa with typical seven transmembrane domain architecture. RcCCR9 shared several conserved structural features with homologs from mammals and other fish, and had a consistent relationship with phylogenetic trees and sequence identities. Reverse transcription quantitative PCR analysis showed ubiquitous RcCCR9 transcripts in healthy cobia, mainly in immune-related organs, with the highest levels in blood and lower levels in intestines and brain. After challenge with inactivated Vibrio harveyi or viral mimic poly I:C, RcCCR9 expression was up-regulated in head kidney and down-regulated in spleen. Compared with poly I:C, V. harveyi induced a stronger up/down-regulation of CCR9 mRNA levels in the central immune organs. RcCCR9 seems to be strongly involved in host defense against bacterial infection. ARTICLE HISTORY

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Section: Tissue Distribution Of the Rcccr9supporting

confidence: 82%

Molecular characterization and expression analysis of the CCR9 gene from cobia (Rachycentron canadum) following bacterial and poly I:C challenge

Deng

Cheng

et al. 2019

Journal of Applied Animal Research

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“…30,31 They often lead to relapsing bouts and chronic courses, and they can progress to fibrosis, often resulting in pharmacologically unmanageable alterations that need to be resolved, finally, by surgical resections. 32,33 There are currently different therapeutic strategies for treating IBDs, but they are associated with several adverse effects. Therefore, there is an ongoing search for new therapies that may be beneficial in treating these chronic diseases.…”

Section: Discussionmentioning

confidence: 99%

Plumericin prevents intestinal inflammation and oxidative stress in vitro and in vivo

et al. 2019

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Inflammatory bowel diseases (IBDs) are characterized by an inflammatory and oxidative stress condition in the intestinal tissue. In this study, we evaluated the effect of plumericin, one of the main bioactive components of Himatanthus sucuuba (Woodson) bark, on intestinal inflammation and oxidative stress, both in vitro and in vivo. The effect of plumericin (0.5‐2 µM) in vitro was evaluated in rat intestinal epithelial cells (IEC‐6) treated with lipopolysaccharides from E. coli (10 μg/mL) plus interferon‐γ (10 U/mL). Moreover, a 2,4,6‐dinitrobenzene sulfonic acid (DNBS)‐induced colitis model was used to evaluate the anti‐inflammatory and antioxidant activity of plumericin (3 mg/kg) in vivo. The results showed that plumericin significantly reduces intestinal inflammatory factors such as tumor necrosis factor‐α, cyclooxygenase‐2 and inducible nitric oxide synthase expression, and nitrotyrosine formation. Plumericin also inhibited nuclear factor‐κB translocation, reactive oxygen species (ROS) release, and inflammasome activation. Moreover, plumericin activated the nuclear factor erythroid‐derived 2 pathway in IEC‐6. Using the DNBS‐induced colitis model, a significant reduction in the weight loss and in the development of the macroscopic and histologic signs of colon injury, together with a reduced inflammatory and oxidative stress state, were observed in plumericin‐treated mice. These results indicate that plumericin exerts a strong anti‐inflammatory and antioxidant activity. Thus, it might be a candidate for the development of a new pharmacologic approach for IBDs treatment.

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“…It is worth noting that GSK/Chemocentryx has advanced its CCR9 antagonist CCX282-B (also known as vercirnon) to a pivotal phase III clinical trial. It was unfortunate that due to poor efficacy of IBD, the clinical project was terminated at the end of 2013 ( Zhang et al, 2015 ).…”

Section: The Role Of Ccr9/ccl25 In Inflammatory Diseasesmentioning

confidence: 99%

The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases

Sun

Yang

et al. 2021

Front. Cell Dev. Biol.

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Chemokine is a structure-related protein with a relatively small molecular weight, which can target cells to chemotaxis and promote inflammatory response. Inflammation plays an important role in aging. C-C chemokine receptor 9 (CCR9) and its ligand C-C chemokine ligand 25 (CCL25) are involved in the regulating the occurrence and development of various diseases, which has become a research hotspot. Early research analysis of CCR9-deficient mouse models also confirmed various physiological functions of this chemokine in inflammatory responses. Moreover, CCR9/CCL25 has been shown to play an important role in a variety of inflammation-related diseases, such as cardiovascular disease (CVD), rheumatoid arthritis, hepatitis, inflammatory bowel disease, asthma, etc. Therefore, the purpose of this review gives an overview of the recent advances in understanding the roles of CCR9/CCL25 in inflammation and inflammation-associated diseases, which will contribute to the design of future experimental studies on the potential of CCR9/CCL25 and advance the research of CCR9/CCL25 as pharmacological inflammatory targets.

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Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease

Cited by 15 publications

References 14 publications

Molecular characterization and expression analysis of the CCR9 gene from cobia (Rachycentron canadum) following bacterial and poly I:C challenge

Molecular characterization and expression analysis of the CCR9 gene from cobia (Rachycentron canadum) following bacterial and poly I:C challenge

Plumericin prevents intestinal inflammation and oxidative stress in vitro and in vivo

The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases

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