Delving into the Latest Updates on CSPCHA115 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

PGD2 receptor

Mechanism

PGD2 receptor antagonists(Prostaglandin D2 receptor antagonists)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesOtorhinolaryngologic Diseases+ [1]

Active Indication-

Inactive Indication

allergic rhinitis with asthmaAsthmaRhinitis, Allergic

Originator Organization

CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.

Active Organization-

Inactive Organization

CSPC Zhongqi Pharmaceutical Technology (Tianjin) Co., Ltd.

CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.

Centaurus Biopharma Co Ltd

Drug Highest PhasePendingPhase 1

First Approval Date-

RegulationSpecial Review Project (CN)

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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。

[Translation]

Primary objective: To evaluate the safety and tolerability of CSPCHA115 capsules after a single oral administration in healthy Chinese subjects. Secondary objective: To evaluate the pharmacokinetic characteristics of CSPCHA115 capsules after a single oral administration in healthy Chinese subjects. Exploratory objective: To analyze the metabolites of CSPCHA115 capsules after a single oral administration in healthy Chinese subjects.

Start Date26 Jul 2018

Sponsor / Collaborator

Centaurus Biopharma Co Ltd

[+1]

100 Clinical Results associated with CSPCHA115

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100 Translational Medicine associated with CSPCHA115

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100 Patents (Medical) associated with CSPCHA115

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3

Literatures (Medical) associated with CSPCHA115

01 Mar 2023·Clinical and Translational Science

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

Article

Author: 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.

01 Mar 2020·Chemistry & BiodiversityQ3 · CHEMISTRY

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

Q3 · CHEMISTRY

Article

Author: 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.

01 Jul 2019·European Journal of Pharmacology

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

Article

Author: 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 Deals associated with CSPCHA115

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
allergic rhinitis with asthma	Phase 1	CN	CSPC Zhongqi Pharmaceutical Technology (Tianjin) Co., Ltd.	12 Dec 2019
Asthma	Phase 1	CN	Centaurus Biopharma Co Ltd	26 Jul 2018
Asthma	Phase 1	CN	CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.	26 Jul 2018
Rhinitis, Allergic	Phase 1	CN	CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.	26 Jul 2018
Rhinitis, Allergic	Phase 1	CN	Centaurus Biopharma Co Ltd	26 Jul 2018