Last update 01 Nov 2024

CRTH2

Last update 01 Nov 2024

Basic Info

Synonyms

CD294, chemoattractant receptor homologous molecule expressed on T helper type 2 cells, Chemoattractant receptor-homologous molecule expressed on Th2 cells

+ [8]

Introduction

Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses.

Drugs associated with CRTH2

ACT-CRTH2

Target

CRTH2

Mechanism

CRTH2 antagonists

Active Org.

Actelion Pharmaceuticals Ltd.

Originator Org.

Actelion Pharmaceuticals Ltd.

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TM-30089

Target

CRTH2

Mechanism

CRTH2 antagonists

Active Org.

7TM A/S

Originator Org.

7TM A/S

Active Indication

Rhinitis, Allergic

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

[18F]-MK-7246

Target

CRTH2

Mechanism

CRTH2 antagonists

Active Org.

University of Uppsala

Originator Org.

University of Uppsala

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

118

Clinical Trials associated with CRTH2

NCT05607446 / Unknown statusPhase 1

A Single-center, Randomized, Double-blind, Two-cycle, Two-way Crossover Phase Ib Study to Evaluate the Efficacy and Safety of TQC3564 Tablets in the Treatment of Persistent Allergic Rhinitis

A clinical study to evaluate the efficacy and safety of tqc3564 tablets in the treatment of persistent allergic rhinitis. A total of 24 patients will be enrolled.

Start Date14 Sep 2022

Sponsor / Collaborator

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

CTR20220964 / TerminatedPhase 1

评价TQC3564片治疗持续性变应性鼻炎的有效性和安全性的单中心、随机、双盲、两周期、两交叉Ib期临床试验

[Translation] A single-center, randomized, double-blind, two-period, two-crossover phase Ib clinical trial to evaluate the efficacy and safety of TQC3564 tablets in the treatment of persistent allergic rhinitis

【第一阶段】主要目的：与安慰剂对照，初步评估TQC3564片治疗持续性变应性鼻炎患者中的有效性。次要目的：与安慰剂对照，初步评估TQC3564片治疗持续性变应性鼻炎患者中的安全性。【第二阶段】主要目的评价TQC3564片联合孟鲁司特钠片治疗持续性变应性鼻炎患者中的有效性。次要目的：评价TQC3564片联合孟鲁司特钠片治疗持续性变应性鼻炎患者中的安全性。

[Translation]

[Phase I] Primary objective: Compared with placebo, preliminarily evaluate the effectiveness of TQC3564 tablets in the treatment of patients with persistent allergic rhinitis. Secondary objective: Compared with placebo, preliminarily evaluate the safety of TQC3564 tablets in the treatment of patients with persistent allergic rhinitis. [Phase II] Primary objective Evaluate the effectiveness of TQC3564 tablets combined with montelukast sodium tablets in the treatment of patients with persistent allergic rhinitis. Secondary objective: Evaluate the safety of TQC3564 tablets combined with montelukast sodium tablets in the treatment of patients with persistent allergic rhinitis.

Start Date17 Aug 2022

Sponsor / Collaborator

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

CTR20192397 / CompletedPhase 1

评价TQC3564在健康受试者中随机、双盲、安慰剂对照的多剂量、单次、多次给药的耐受性、药代动力学Ⅰa期临床试验

[Translation] A randomized, double-blind, placebo-controlled phase Ia clinical trial to evaluate the tolerability and pharmacokinetics of TQC3564 in healthy subjects with multiple doses, single doses, and multiple administrations

评价TQC3564在健康受试者中多剂量、单次、多次给药耐受性；评价 TQC3564在健康受试者中多剂量、单次、多次给药药代动力学；评价 TQC3564 药物代谢转化研究；评价食物对TQC3564药代动力学的影响。

[Translation]

To evaluate the tolerance of TQC3564 in healthy subjects after multiple doses, single doses and multiple administrations; To evaluate the pharmacokinetics of TQC3564 in healthy subjects after multiple doses, single doses and multiple administrations; To evaluate the drug metabolism and transformation study of TQC3564; To evaluate the effect of food on the pharmacokinetics of TQC3564.

Start Date19 Nov 2019

Sponsor / Collaborator

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

100 Clinical Results associated with CRTH2

100 Translational Medicine associated with CRTH2

0 Patents (Medical) associated with CRTH2

1,116

Literatures (Medical) associated with CRTH2

01 Nov 2024·Ecotoxicology and Environmental Safety

Unraveling cadmium-driven liver inflammation with a focus on arachidonic acid metabolites and TLR4/ IκBα /NF-κB pathway

Article

Author: Gong, Xun ; Liu, Junlin ; Guo, Chuanzhi ; Shi, Haifeng ; Tang, Min ; Gu, Jie ; Ruan, Jiacheng ; Li, Zehua

Epidemiological studies have demonstrated exposure to cadmium ion (Cd²⁺) is significantly associated with the incidence and aggravation of nonalcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Cd²⁺ exposure could alter lipid metabolism, and changed lipid metabolites are significantly associated with NASH. Arachidonic acid (ArA) is an omega-6 polyunsaturated fatty acid. Promotion of ArA synthesis and profile changes by Cd²⁺ exposure potentially to cause NAFLD. ArA metabolism pathway has been identified to enrich in Cd²⁺ exposure-facilitated NASH. ArA could be generation an impressive metabolic profile through mainly three pathways, including Cyclooxygenases (COX), Lipoxygenases (LOX) and Cytochrome P450 (CYP450) pathway. However, the functions of these metabolites and underlying mechanism in hepatic inflammation are still not clear. In present study, by integrative transcriptomics and metabolomics analysis, we identified that the fatty acid metabolic process and the pro-inflammatory NF-κB signaling pathway were enriched in Cd²⁺-regulated differentially expressed genes (DEGs) and Cd²⁺-altered differential metabolites, such as, fatty acid biosynthesis, degradation, and ArA metabolism. The metabolites levels of LOX pathway products 5-HETE and leukotriene C4 (LTC4), and COX catalytic product prostaglandin D2 (PGD2) were significantly elevated in Cd²⁺ exposed mouse livers. 5-HETE, LTC4, and PGD2 were significantly positive correlated with NF-κB signaling. In addition, the synthase of 20-Hydroxyeicosatetraenoic acid (20-HETE), CYP450 gene 4 family (CYP4A32), was also involved in NF-κB signaling network. Results from both in vitro and in vivo proved that Cd²⁺ exposure increased ArA metabolite to PGD2 and 20-HETE, and upregulated the mRNA level of their catalytic enzyme PGDS and CYP4A32. Cd²⁺-induced ArA metabolite to PGD2 and 20-HETE promoted activation of TLR4/IκBα/NF-κB signaling and pro-inflammatory of hepatocytes. Our study explores novel molecular mechanism of Cd²⁺ exposure-aggravated liver diseases and provides potential novel targets for in hepatic inflammatory treatments and prevention.

04 Oct 2024·Rhinology

Blood transcriptomics reveal systemic eosinophilic and neutrophilic inflammation patterns in patients with nasal polyps.

Article

Author: Sun, Y ; Guan, H ; Wang, K ; Cui, Y ; Liu, C ; Fan, Y ; Shi, J ; Liu, W ; Ma, L

BACKGROUNDChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal disease characterized by heterogeneous inflammation. However, the presence of systemic inflammation heterogeneity in CRSwNP patients remains unknown. This study aims to profile transcriptomic alterations in the blood of CRSwNP patients and characterize the CRSwNP heterogeneity based on blood transcriptomic biomarkers.METHODOLOGYPatients with CRSwNP were prospectively recruited from three hospitals and chronologically divided into exploratory (n=123) and independent validation (n=46) cohorts. Transcriptomic profiles were generated by whole blood mRNA sequencing and subjected to patient clustering, differential expression, and pathway analysis. Differences in immune pattern and clinicopathologic features between clusters were assessed. A transcriptomic signature was defined and applied to an independent cohort to validate the findings.RESULTSCRSwNP patients showed diverse blood transcriptomic profiles versus healthy controls, or when stratified by tissue and blood eosinophils and asthma comorbidity. Transcriptome-wide correlation analysis revealed a transcriptional signature associated with blood eosinophil levels, consisting of nine T2-related genes (CLC, SIGLEC8, ALOX15, IL5RA, PTGDR2, CCL23, CCR3, EPX and IL1RL1). Three distinct clusters with differing systemic eosinophilic and neutrophilic inflammation patterns and asthma comorbidity were identified based on transcriptomic profiling of T2 and T1/3-related blood biomarkers. A 36-gene signature was developed by machine learning and accurately predicted the three CRSwNP subtypes. Validation on an independent cohort confirmed the prediction robustness.CONCLUSIONSThere is heterogeneous systemic inflammation associated with eosinophilic and neutrophilic patterns in patients with CRSwNP. Endotyping based on blood transcriptomic biomarkers might lead to more personalized treatment strategies for CRSwNP in the future.

02 Oct 2024·Journal of Asthma

Analysis of the potential molecular mechanisms of asthma and gastroesophageal reflux disease

Article

Author: Zhang, Wen ; Jiang, Chenglin ; Chen, Changdan ; Zhang, Wei ; Zheng, Xiujin

OBJECTIVEAsthma and gastroesophageal reflux disease (GERD) often occur simultaneously, with GERD being a comorbidity of asthma. This study aimed to explore the biological markers related to asthma and GERD by bioinformatics analysis.METHODSInitially, gene expression datasets for asthma and GERD were obtained from the Gene Expression Omnibus database, and subsequent differential expression analysis yielded 620 differentially expressed genes (DEGs) for asthma and 2367 DEGs for GERD. The intersection of these two gene sets yielded a total of 84 DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these genes may be involved in steroid hormone secretion and cellular stress response. Five hub genes (PTGDR2, CPA3, FCER1A, TPSAB1, and IL1RL1) were identified by a protein-protein interaction (PPI) network analysis and topological algorithm.RESULTSEnrichment analysis results indicated that hub genes may be involved in hormone secretion and disease development, particularly in regulating the renin-angiotensin system and systemic arterial blood pressure. PTGDR2, CPA3, TPSAB1, and IL1RL1 were upregulated in both asthma and GERD patient groups, while FCER1A was upregulated in asthma patients but downregulated in GERD patients. Through drug prediction, 22 drugs targeting hub genes PTGDR2, FCER1A, and TPSAB1 were identified. By constructing a transcription factor (TF)-target gene network, we found that eight TFs may regulate the expression of PTGDR2, FCER1A, and IL1RL1.CONCLUSIONHence, Asthma and GERD were related to steroid hormone secretion and the renin-angiotensin system.

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CRTH2

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