CPL-207-280(CPL-207-280) - 药物靶点：GPR40_在研适应症：2型糖尿病，糖尿病性神经病变_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [2]

靶点

GPR40

作用方式

激动剂

作用机制

GPR40激动剂(游离脂肪酸受体-1激动剂)

治疗领域

神经系统疾病内分泌与代谢疾病

在研适应症

2型糖尿病糖尿病性神经病变

非在研适应症-

原研机构

Celon Pharma SA

在研机构

Celon Pharma SA

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

3

项与 CPL-207-280 相关的临床试验

NCT05248776

/ Recruiting临床2期

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate Efficacy, Safety and Pharmacokinetics After 2-weeks Administration of CPL207280 (GPR40 Agonist) in Subjects With Type 2 Diabetes (T2D)

The planned study is to evaluate the efficacy, safety and pharmacokinetic (PK) properties of CPL207280 after multiple (14 days) administration in patients with type 2 diabetes.

开始日期2022-01-21

申办/合作机构

Celon Pharma SA

[+1]

EUCTR2021-002947-32-PL

/ Not yet recruiting临床2期

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate Efficacy, Safety and Pharmacokinetics after 2-weeks Administration of CPL207280 (GPR40 agonist) in Subjects With Type 2 Diabetes (T2D)

开始日期2021-10-28

申办/合作机构

Celon Pharma SA

NCT04622111

/ Completed临床1期

One Centre, Single Ascending Dose and Double Blind Multiple Ascending Dose, Safety and Pharmacokinetics Phase I Study of CPL207280 Compound in Healthy Volunteers.

The planned study is to determine the safety and pharmacokinetic properties of CPL207280 compound after single and multiple (two weeks) administration in healthy volunteers.

开始日期2020-05-27

申办/合作机构

Celon Pharma SA

[+1]

100 项与 CPL-207-280 相关的临床结果

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100 项与 CPL-207-280 相关的转化医学

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100 项与 CPL-207-280 相关的专利（医药）

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5

项与 CPL-207-280 相关的文献（医药）

2024-04-01·Diabetes, Obesity and Metabolism

First‐in‐human study of CPL207280, a novel G‐protein‐coupled receptor 40/free fatty acid receptor 1 agonist, in healthy volunteers after single and multiple administration

Article

作者: Jarus-Dziedzic, Katarzyna ; Buda, Paweł ; Tratkiewicz, Ewa ; Wieczorek, Maciej ; Gierczak-Pachulska, Agnieszka ; Bazydło-Guzenda, Katarzyna ; Juszczyk, Ewelina ; Buś-Kwaśnik, Katarzyna ; Segiet-Święcicka, Agnieszka ; Rudzki, Piotr J ; Rabczenko, Daniel

AbstractAimTo assess the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of CPL207280, a new G‐protein‐coupled receptor 40 agonist developed to treat type 2 diabetes (T2D).MethodsThe phase 1 study in healthy volunteers (White, age 18–55 years, body mass index 18.5–29.9 kg/m2) was performed after single (24 subjects, 5–480 mg) and multiple (32 subjects, 60–480 mg) once‐daily administration of CPL207280. The effect of food intake and interaction with metformin were evaluated in additional cohort (12 subjects, 120 mg). The primary objective was the safety and tolerability of CPL207280. Secondary objectives included PK and pharmacodynamic (PD) characteristics (glucose, insulin, C‐peptide, proinsulin, glucagon levels) observed during the 14‐day treatment period.ResultsNo deaths or serious adverse events (AEs) were reported. All reported AEs were classified as unrelated to the study product. No clinically significant differences in safety parameters were observed between cohorts and no food or metformin effect on safety parameters was identified. The ascending dose of CPL207280 caused an increase in the PK parameters maximum observed plasma concentration (Cmax) or area under the plasma concentration–time curve up to 24 h. However, dose‐normalized Cmax decreased with ascending dose. There was no relationship between the CPL207280 dose or prandial state and terminal elimination half‐life and terminal elimination rate constant. No clear relationship between CPL207280 dose and PD area under the effect curve values was observed.ConclusionsCPL207280 was found to be safe and well tolerated by healthy volunteers (with a low risk of hepatotoxicity) for up to 14 days of administration. The PK profile of CPL207280 supports single‐daily administration and justifies further development of this therapy for patients with T2D.

2021-12-01·European Journal of Medicinal Chemistry1区 · 医学

Discovery and development of CPL207280 as new GPR40/FFA1 agonist

1区 · 医学

Article

作者: Bazydło-Guzenda, Katarzyna ; Dubiel, Krzysztof ; Dawid, Urszula ; Dzida, Radosław ; Smuga, Damian ; Hołowińska, Dagmara ; Gurba-Bryśkiewicz, Lidia ; Stelmach, Filip ; Wiśniewski, Krzysztof ; Buda, Paweł ; Gałązka, Kinga ; Mach, Mateusz ; Pieczykolan, Jerzy ; Matłoka, Mikołaj ; Wieczorek, Maciej ; Wąsińska-Kałwa, Małgorzata

Due to a unique mechanism that limits the possibility of hypoglycemia, the free fatty acid receptor (FFA1) is an attractive target for the treatment of type 2 diabetes. So far, however, none of the promising agonists have been able to enter the market. The most advanced clinical candidate, TAK-875, was withdrawn from phase III clinical trials due to liver safety issues. In this article, we describe the key aspects leading to the discovery of CPL207280 (13), the design of which focused on long-term safety. The introduction of small, nature-inspired acyclic structural fragments resulted in compounds with retained high potency and a satisfactory pharmacokinetic profile. Optimized synthesis and upscaling provided a stable, solid form of CPL207280-51 (45) with the properties required for the toxicology studies and ongoing clinical trials.

2021-10-01·Molecular Pharmacology

CPL207280, a Novel G Protein–Coupled Receptor 40/Free Fatty Acid Receptor 1–Specific Agonist, Shows a Favorable Safety Profile and Exerts Antidiabetic Effects in Type 2 Diabetic Animals

Article

作者: Bazydlo-Guzenda, Katarzyna ; Wieczorek, Maciej ; Pieczykolan, Jerzy ; Kaminska, Bozena ; Teska-Kaminska, Malgorzata ; Dzida, Radoslaw ; Matloka, Mikolaj ; Stelmach, Filip ; Smuga, Damian ; Mach, Mateusz ; Dubiel, Krzysztof ; Vialichka, Varvara ; Hucz-Kalitowska, Joanna ; Buda, Pawel

G protein-coupled receptor (GPR) 40 is a free fatty acid receptor mainly expressed in pancreatic β-cells activated by medium- and long-chain fatty acids and regulating insulin secretion via an increase in cytosolic free calcium ([Ca²⁺]_i). Activation of GPR40 in pancreatic β-cells may improve glycemic control in type 2 diabetes through enhancement of glucose-stimulated insulin secretion. However, the most clinically advanced GPR40 agonist-TAK-875 (fasiglifam)-was withdrawn from phase III because of its hepatotoxicity resulting from the inhibition of pivotal bile acid transporters. Here, we present a new, potent CPL207280 agonist and compare it with fasiglifam in numerous in vitro and in vivo studies. CPL207280 showed greater potency than fasiglifam in a Ca²⁺ influx assay with a human GPR40 protein (EC₅₀ = 80 vs. 270 nM, respectively). At the 10 µM concentration, it showed 3.9 times greater enhancement of glucose-stimulated insulin secretion in mouse MIN6 pancreatic β-cells. In Wistar Han rats and C57BL6 mice challenged with glucose, CPL207280 stimulated 2.5 times greater insulin secretion without causing hypoglycemia at 10 mg/kg compared with fasiglifam. In three diabetic rat models, CPL207280 improved glucose tolerance and increased insulin area under the curve by 212%, 142%, and 347%, respectively. Evaluation of potential off-target activity (Safety47) and selectivity of CPL207280 (at 10 μM) did not show any significant off-target activity. We conclude that CPL207280 is a potent enhancer of glucose-stimulated insulin secretion in animal disease models with no risk of hypoglycemia at therapeutic doses. Therefore, we propose the CPL207280 compound as a compelling candidate for type 2 diabetes treatment. SIGNIFICANCE STATEMENT: GPR40 is a well-known and promising target for diabetes. This study is the first to show the safety and effects of CPL207280, a novel GPR40/free fatty acid receptor 1 agonist, on glucose homeostasis both in vitro and in vivo in different diabetic animal models. Therefore, we propose the CPL207280 compound as a novel, glucose-lowering agent, overcoming the unmet medical needs of patients with type 2 diabetes.

100 项与 CPL-207-280 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床2期	波兰	Celon Pharma SA	2022-01-21
糖尿病性神经病变	临床2期	-	Celon Pharma SA	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04622111 (Phase 1, EASD2021)	临床1期	-	32	CPL207280 60 mg	願鏇繭廠構構蓋醖憲獵(鏇窪獵積簾鹽糧獵餘顧) = The administration of CPL207280 was generally safe and well-tolerated with no serious AEs. All adverse events were classified as not related to the study product. No increase in the tested hepatic parameters (ALT, AST, ALP, bilirubin, creatinine) was observed. There were no hypoglycaemia episodes during the study. 鏇壓網襯願齋鏇製淵積 (築網製餘壓窪壓積鏇窪 )	积极	2021-10-01
				CPL207280 480 mg
NCT04622111 (CPL207280, Pubmed \| Mol Pharmacol)	临床1期	-	68	CPL207280	醖鹽鹽築鬱憲餘觸鑰淵(鬱製範鏇餘簾鹽鏇簾膚) = 醖襯範構獵壓壓構艱構簾齋廠餘鹹憲襯顧膚願 (艱衊憲願觸餘製鹹獵蓋 ) 更多	-	2021-08-04
EASD2018	N/A	糖尿病 Ca 2+	-	CPL207-280CA	糧製鏇鹽醖膚膚獵糧淵(製觸鏇餘鹽鹹餘鏇壓淵) = 淵願觸繭膚淵餘積構獵夢願淵選顧窪糧選衊繭 (壓鏇構廠範網顧窪網築 )	积极	2018-10-03
				Fasiglifam	糧製鏇鹽醖膚膚獵糧淵(製觸鏇餘鹽鹹餘鏇壓淵) = 齋膚醖繭膚窪觸顧願糧夢願淵選顧窪糧選衊繭 (壓鏇構廠範網顧窪網築 )