CPL-500036(CPL-500036) - 药物靶点：PDE10A_在研适应症：药物性运动障碍，帕金森病，精神分裂症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [4]

靶点

PDE10A

作用机制

PDE10A抑制剂(磷酸二酯酶10A抑制剂)

治疗领域

神经系统疾病内分泌与代谢疾病其他疾病

在研适应症

药物性运动障碍帕金森病精神分裂症

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

5

项与 CPL-500036 相关的临床试验

NCT05297201 / Recruiting临床2期

Phase II, Double Blind, Randomized, Placebo Controlled, Parallel Group, Trial to Explore the Potential Anti-dyskinetic Properties of CPL500036 (PDE10A Inhibitor) in Patients With Parkinson's Disease Suffering From Levodopa Induced Dyskinesia

The aim of the study is to determine potential anti-dyskinetic properties of CPL500036 (PDE10A inhibitor) in Parkinson disease patients suffering from levodopa Induced dyskinesia. The study is to determine the efficacy and dose response of two CPL500036 doses, compared with placebo.

开始日期2021-11-02

申办/合作机构

Celon Pharma SA

[+1]

EUCTR2020-006004-16-PL / Unknown status临床2期

Phase II, Double blind, Randomized, Placebo controlled, Parallel group, Trial to Explore the Potential Anti-dyskinetic Properties of CPL500036 (PDE10A inhibitor) in Patients with Parkinson's Disease Suffering from Levodopa Induced Dyskinesia

开始日期2021-07-16

申办/合作机构

Celon Pharma SA

NCT05278156 / Completed临床2期

Phase II, Double Blind, Randomized, Placebo Controlled, Parallel Group, Trial to Explore Efficacy, Safety and Pharmacokinetics of CPL500036 (PDE10A Inhibitor) in Patients With an Acute Exacerbation of Schizophrenia

The purpose of this study is to determine the efficacy, safety, tolerability and pharmacokinetics (PK) properties of CPL500036 compound (PDE10a inhibitor) in patients with an acute exacerbation of schizophrenia after 28 days of administration..

开始日期2021-05-19

申办/合作机构

Celon Pharma SA

[+1]

100 项与 CPL-500036 相关的临床结果

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100 项与 CPL-500036 相关的转化医学

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100 项与 CPL-500036 相关的专利（医药）

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2

项与 CPL-500036 相关的文献（医药）

2021-11-01·European Journal of Pharmacology3区 · 医学

Antiparkinsonian-like effects of CPL500036, a novel selective inhibitor of phosphodiesterase 10A, in the unilateral rat model of Parkinson's disease

3区 · 医学

Article

作者: Wieczorek, Maciej ; Ossowska, Krystyna ; Pieczykolan, Jerzy ; Matłoka, Mikołaj ; Konieczny, Jolanta ; Lenda, Tomasz ; Berghauzen-Maciejewska, Klemencja

Phosphodiesterase 10A (PDE10A), the enzyme which catalyzes hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), is located almost exclusively in striatal γ-amino-butyric acid (GABA)ergic medium spiny neurons (MSNs). Since dopaminergic deficiency in Parkinson's disease (PD) leads to functional imbalance of striatal direct and indirect output pathways formed by MSNs, PDE10A seems to be of special interest as a potential therapeutic target in PD. The aim of the present study was to examine the influence of 7-{5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl}-2-phenylimidazo[1,2-a]pyrimidine (CPL500036), a novel selective inhibitor of PDE10A, on sensorimotor deficits and therapeutic effects of L-3,4-dihydroxyphenylalanine (L-DOPA) in hemiparkinsonian rats. Animals were unilaterally lesioned with 6-hydroxydopamine, and their sensorimotor deficits were examined in the stepping, cylinder, vibrissae and catalepsy tests. CPL500036 (0.1 and 0.3 mg/kg) was administered either acutely or chronically (2 weeks), alone or in combination with L-DOPA/benserazide (6 mg/kg/6 mg/kg). Acute treatment with CPL500036 reversed the lesion-induced impairments of contralateral forelimb use in the stepping and cylinder tests but did not influence deficits in the vibrissae test and the lesion-induced catalepsy. Moreover, CPL500036 did not diminish the therapeutic effects produced by acute and chronic treatment with L-DOPA in these tests. The present study suggests a potential use of CPL500036 as a co-treatment to L-DOPA in PD therapy.

Frontiers in Pharmacology

A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects

Article

作者: Jakubowski, Piotr ; Dera, Paulina ; Bojarski, Lukasz ; Janicka, Monika ; Popik, Piotr ; Welniak-Kaminska, Marlena ; Hołuj, Małgorzata ; Abramski, Krzysztof ; Kos, Tomasz ; Pieczykolan, Jerzy ; Hucz-Kalitowska, Joanna ; Kokhanovska, Sofiya ; Janowska, Sylwia ; Rutkowska-Wlodarczyk, Izabela ; Matloka, Mikolaj ; Świątkiewicz, Maciej ; Wieczorek, Maciej ; Grieb, Paweł ; Pankiewicz, Piotr

Background: Phosphodiesterase 10A (PDE10A) is expressed almost exclusively in the striatum and its inhibition is suggested to offer potential treatment in disorders associated with basal ganglia. We evaluated the selectivity, cytotoxicity, genotoxicity, pharmacokinetics and potential adverse effects of a novel PDE10A inhibitor, CPL500036, in vivo.Methods: The potency of CPL500036 was demonstrated by microfluidic technology, and selectivity was investigated in a radioligand binding assay against 44 targets. Cardiotoxicity in vitro was evaluated in human ether-a-go-go related gene (hERG)-potassium channel-overexpressing cells by the patch-clamp method and by assessing key parameters in 3D cardiac spheroids. Cytotoxicity was determined in H1299, HepG2 and SH-SY5Y cell lines. The Ames test was used for genotoxicity analyses. During in vivo studies, CPL500036 was administered by oral gavage. CPL500036 exposure were determined by liquid chromatography–tandem mass spectrometry and plasma protein binding was assessed. The bar test was employed to assess catalepsy. Prolactin and glucose levels in rat blood were measured by ELISAs and glucometers, respectively. Cardiovascular safety in vivo was investigated in dogs using a telemetry method.Results: CPL500036 inhibited PDE10A at an IC50 of 1 nM, and interacted only with the muscarinic M2 receptor as a negative allosteric modulator with an IC50 of 9.2 µM. Despite inhibiting hERG tail current at an IC25 of 3.2 μM, cardiovascular adverse effects were not observed in human cardiac 3D spheroids or in vivo. Cytotoxicity in vitro was observed only at > 60 μM and genotoxicity was not recorded during the Ames test. CPL500036 presented good bioavailability and penetration into the brain. CPL500036 elicited catalepsy at 0.6 mg/kg, but hyperprolactinemia or hyperglycemic effects were not observed in doses up to 3 mg/kg.Conclusion: CPL500036 is a potent, selective and orally bioavailable PDE10A inhibitor with a good safety profile distinct from marketed antipsychotics. CPL500036 may be a compelling drug candidate.

100 项与 CPL-500036 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
药物性运动障碍	临床2期	乌克兰	Celon Pharma SA	2021-11-02
药物性运动障碍	临床2期	波兰	Celon Pharma SA	2021-11-02
帕金森病	临床2期	波兰	Celon Pharma SA	2021-11-02
帕金森病	临床2期	乌克兰	Celon Pharma SA	2021-11-02
精神分裂症	临床2期	波兰	Celon Pharma SA	2021-05-19
精神分裂症	临床2期	乌克兰	Celon Pharma SA	2021-05-19
精神分裂症	临床2期	匈牙利	Celon Pharma SA	2021-05-19

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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


NCT05278156 (Company_Website) 人工标引	临床2期	急性精神分裂症	189	CPL' 36 (20mg)	(鹹窪淵鏇壓積製築鹹築) = 襯憲願糧構鏇衊糧壓鬱顧糧鏇膚襯獵壓鬱鹽衊 (鹹網製繭淵餘壓願壓衊 ) 更多	积极	2024-07-05
				CPL' 36 (40 mg)	(鹹窪淵鏇壓積製築鹹築) = 製窪蓋範膚繭顧鏇艱製顧糧鏇膚襯獵壓鬱鹽衊 (鹹網製繭淵餘壓願壓衊 ) 更多