CSPCHA115(CSPCHA115) - 药物靶点：PGD2 receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PGD2 receptor

作用机制

PGD2 receptor拮抗剂(前列腺素D2受体拮抗剂)

治疗领域

免疫系统疾病呼吸系统疾病

在研适应症-

非在研适应症

过敏性鼻炎伴哮喘

原研机构

石药集团中奇制药技术（石家庄）有限公司

在研机构-

非在研机构

北京赛林泰医药技术有限公司

石药集团中奇制药技术（石家庄）有限公司

石药集团中奇制药技术（天津）有限公司

最高研发阶段无进展临床1期

首次获批日期-

最高研发阶段(中国)无进展

特殊审评特殊审批 (中国)

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关联

3

项与 CSPCHA115 相关的临床试验

CTR20191985 / Completed临床1期

CSPCHA115 胶囊多次给药在中国健康受试者中的耐受性、药代动力学I期临床试验

评价中国健康受试者多次口服CSPCHA115胶囊后的耐受性及药代动力学特征。

开始日期2019-12-13

申办/合作机构

北京赛林泰医药技术有限公司

[+1]

NCT04161547 / Completed临床1期

A Phase I, Ascending Multiple-dose Clinical Trial of CSPCHA115 Capsules to Evaluate the Tolerability and Pharmacokinetics in Chinese Healthy Volunteers

A randomized, single-center, double-blind, ascending multiple-dose, placebo-controlled study to evaluate the tolerability and pharmacokinetics of CSPCHA115 capsules in Chinese healthy volunteers.

开始日期2019-12-12

申办/合作机构

石药集团中奇制药技术（天津）有限公司

CTR20180984 / Completed临床1期

CSPCHA115胶囊在健康受试者中的Ⅰ期安全性、耐受性及药代动力学临床试验

主要目的——评价中国健康受试者单次口服CSPCHA115胶囊后的安全性和耐受性。次要目的——评价中国健康受试者单次口服CSPCHA115胶囊后的药代动力学特征。探索性目的——中国健康受试者单次口服CSPCHA115胶囊后的代谢产物分析。

开始日期2018-07-26

申办/合作机构

北京赛林泰医药技术有限公司

[+1]

100 项与 CSPCHA115 相关的临床结果

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100 项与 CSPCHA115 相关的转化医学

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100 项与 CSPCHA115 相关的专利（医药）

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3

项与 CSPCHA115 相关的文献（医药）

2023-03-01·Clinical and Translational Science

The randomized, single‐ and multiple‐ ascending dose studies of the safety, tolerability, pharmacokinetics of CSPCHA115 in healthy Chinese subjects

Article

作者: Sun, Guilan ; Yang, Kexu ; Jing, Shan ; Lin, Yang ; Liu, Wenfang ; Yao, Xuekun

AbstractCSPCHA115 is a highly selective and potent antagonist of chemoattractant receptor‐homologous molecule expressed on TH2 cells (CRTH2). This study aimed to evaluate the pharmacokinetics (PKs), safety, and tolerability of single and multiple ascending doses of CSPCHA115 in Chinese healthy subjects. Two phase I studies both adopted a randomized, double‐blind, placebo‐controlled, single‐center, and ascending‐dose design. In the single ascending dose (SAD) study, subjects were randomly allocated to receive a single dose of CSPCHA115 (25–1000 mg) or a placebo. In the multiple ascending dose (MAD) study, 100, 200, 400, or 600 mg of CSPCHA115 or placebo were given to subjects once daily for 7 days. PK parameters were estimated by noncompartmental analysis. Safety was assessed by monitoring treatment‐emergent adverse events (TEAEs), clinical laboratory tests, electrocardiograms, vital signs, and physical examinations throughout the study period. Forty‐eight healthy subjects were enrolled in the SAD study, and 40 healthy subjects were in the MAD study. Following single and multiple administrations, CSPCHA115 was rapidly absorbed with a median time to maximum concentration of ~0.5–3.5 h; and the systemic exposure of CSPCHA115 generally increased dose‐proportionally within the dose range studied. Steady‐state was approximately achieved by day 5, and <1.5‐fold accumulation was observed following multiple doses. Mean terminal half‐life was ~8.16–16.43 h after a single dose. CSPCHA115 was well‐tolerated in both studies, with a low overall incidence of TEAEs. The most common TEAE related to CSPCHA115 was hypertriglyceridemia. No significant safety concerns were identified in healthy subjects.

2020-03-01·Chemistry & Biodiversity3区 · 化学

Lipid‐Embedded Molecular Dynamics Simulation Model for Exploring the Reverse Prostaglandin D2 Agonism of CT‐133 towards CRTH2 in the Treatment of Type‐2 Inflammation Dependent Diseases

3区 · 化学

Article

作者: Olotu, Fisayo A. ; Soliman, Mahmoud E. S. ; Kumi, Ransford O. ; Issahaku, Abdul Rashid ; Agoni, Clement

AbstractChemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTH2) has been involved in several inflammation dependent diseases by mediating the chemotaxis of pro‐inflammatory cells in response to allergy and other responses through PGD2 ligation. This CRTH2‐PGD2 signaling pathway has become a target for treating allergic and type 2 inflammation dependent diseases, with many inhibitors developed to target the PGD2 binding pocket. One of such inhibitors is the ramatroban analog, CT‐133, which exhibited therapeutic potency cigarette smoke‐induced acute lung injury in patients. Nonetheless, the molecular mechanism and structural dynamics that accounts for its therapeutic prowess remain unclear. Employing computational tools, this study revealed that although the carboxylate moiety in CT‐133 and the native agonist PGD2 aided in their stability within the CRTH2 binding pocket, the tetrahydrocarbazole group of CT‐133 engaged in strong interactions with binding pocket residues which could have formed as the basis of the antagonistic advantage of CT‐133. Tetrahydrocarbazole group interactions also enhanced the relative stability CT‐133 within the binding pocket which consequently favored CT‐133 binding affinity. CT‐133 binding also induced an inactive or ‘desensitized’ state in the helix 8 of CRTH2 which could conversely favor the recruitment of arrestin. These revelations would aid in the speedy development of small molecule inhibitors of CRTH2 in the treatment of type 2 inflammation dependent diseases.

2019-07-01·European Journal of Pharmacology

A CRTH2 antagonist, CT-133, suppresses NF-κB signalling to relieve lipopolysaccharide-induced acute lung injury

Article

作者: Wu, Junsong ; Wu, Ximei ; Xu, Chengyun ; Tang, Lanfang ; Wu, Xiling ; Hussain, Musaddique ; Wu, Fugen ; Lu, Meiping

Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions that still have no definite pharmacotherapy. Hence, we investigate the potential effectiveness and underlying mechanism of CT-133, a newly developed selective antagonist of prostaglandin D2 receptor 2 (DP2) or of chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2), against lipopolysaccharide (LPS)-induced ALI. CT-133 (10 or 30 mg/kg) or dexamethasone (1 mg/kg, positive control) were intragastrically administered 1 h before and 12 h after intratracheal LPS instillation, and primary neutrophils and macrophages and RAW264.7 macrophages were used to investigate the role of CT-133 in regulation of their functions. LPS induced a significant secretion of PGD₂ from primary macrophages, however, CT-133 dose-dependently and markedly decreased the infiltration of neutrophils and macrophages into lungs, reduced the IL-1β, TNF-α, IL-6, and KC levels in broncho-alveolar lavage (BAL) fluids, decreased the wet weight and myeloperoxidase activity of lungs, reduced Evans blue and albumin exudation into lungs, and improved the lung histopathological changes and hypoxemia. Moreover, CT-133 significantly suppressed the primary neutrophil migration toward the PGD₂ and robustly inhibited the mRNA and protein expression of IL-1β, TNF-α, IL-6, and KC in primary and RAW264.7 macrophages in response to either LPS- or PGD₂ stimulation. Finally, CT-133 significantly blocked the LPS-induced P65 activation in both RAW264.7 macrophages and mouse lungs. Thus, This is the first report that a CRTH2 antagonist, CT-133, is capable of significantly alleviating LPS-induced lung injury by probably down-regulating the NF-κB signalling.

100 项与 CSPCHA115 相关的药物交易

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