Ceralifimod(Ceralifimod) - 药物靶点：S1PR1 x S1PR5_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

S1PR1 x S1PR5

作用方式

激动剂

作用机制

S1PR1激动剂(鞘氨醇-1-磷酸受体-Edg-1激动剂)、S1PR5激动剂(鞘氨醇-1-磷酸受体-Edg-8激动剂)

治疗领域

免疫系统疾病神经系统疾病其他疾病

在研适应症-

非在研适应症

复发-缓解型多发性硬化

原研机构

Ono Pharmaceutical Co., Ltd.

在研机构-

非在研机构

Merck KGaA

Ono Pharmaceutical Co., Ltd.

权益机构

Ono Pharmaceutical Co., Ltd.Merck Serono SA

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C27H33NO4

InChIKeyQDDQIPUKAXBMBX-UHFFFAOYSA-N

CAS号891859-12-4

关联

4

项与 Ceralifimod 相关的临床试验

JPRN-jRCT2080221270

/ Unknown status临床2期

A Safety and Efficacy Extension Study of ONO-4641 in Patients with Relapsing-Remitting Multiple Sclerosis

开始日期2010-10-18

申办/合作机构

Ono Pharmaceutical Co., Ltd.

JPRN-JapicCTI-101307

/ Unknown status临床2期

A Safety and Efficacy Extension Study of ONO-4641 in Patients with Relapsing-Remitting Multiple Sclerosis

开始日期2010-10-01

申办/合作机构

Ono Pharmaceutical Co., Ltd.

NCT01226745

/ Terminated临床2期

A Safety and Efficacy Extension Study of ONO-4641 (MSC2430913A) in Patients With Relapsing-Remitting Multiple Sclerosis

The objective of this active-drug Extension Study is to evaluate the continuing safety and efficacy of ONO-4641 (MSC2430913A) in subjects with relapsing-remitting multiple sclerosis (RRMS) who have completed an initial 26-week Core Study (ONO-4641POU006 [NCT01081782]).

开始日期2010-10-01

申办/合作机构

EMD Serono, Inc.

[+2]

100 项与 Ceralifimod 相关的临床结果

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100 项与 Ceralifimod 相关的转化医学

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100 项与 Ceralifimod 相关的专利（医药）

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14

项与 Ceralifimod 相关的文献（医药）

2021-02-01·The Journal of Pharmacology and Experimental Therapeutics3区 · 医学

Sphingosine 1-Phosphate Receptor Modulator ONO-4641 Regulates Trafficking of T Lymphocytes and Hematopoietic Stem Cells and Alleviates Immune-Mediated Aplastic Anemia in a Mouse Model

3区 · 医学

Article

作者: Katsumata, Seishi ; Gohda, Masashi ; Shioya, Hiroki ; Komiya, Takaki

ONO-4641 is a second-generation sphingosine 1-phosphate (S1P) receptor modulator that exhibits selectivity for S1P receptors 1 and 5. Treatment with ONO-4641 leads to a reduction in magnetic resonance imaging disease measures in patients with relapsing-remitting multiple sclerosis. The objective of this study was to explore the potential impact of ONO-4641 treatment based on its immunomodulatory effects. Severe aplastic anemia is a bone marrow (BM) failure disease typically caused by aberrant immune destruction of blood progenitors. Although the T helper type 1-mediated pathology is well described for aplastic anemia, the molecular mechanisms driving disease progression remain undefined. We evaluated the efficacy of ONO-4641 in a mouse model of aplastic anemia. ONO-4641 reduced the severity of BM failure in a dose-dependent manner, resulting in higher blood and BM cell counts. By evaluating the mode of action, we found that ONO-4641 inhibited the infiltration of donor-derived T lymphocytes to the BM. ONO-4641 also induced the accumulation of hematopoietic stem cells in the BM of model mice. These observations indicate, for the first time, that S1P receptor modulators demonstrate efficacy in the mouse model of aplastic anemia and suggest that treatment with ONO-4641 might delay the progression of aplastic anemia. SIGNIFICANCE STATEMENT: ONO-4641 is a second-generation sphingosine 1-phosphate (S1P) receptor modulator selective for S1P receptors 1 and 5. In this study, we demonstrated that ONO-4641 regulates the trafficking of T lymphocytes along with hematopoietic stem and progenitor cells, leading to alleviation of pancytopenia and destruction of bone marrow in a bone marrow failure-induced mouse model mimicking human aplastic anemia.

2021-02-01·Biological and Pharmaceutical Bulletin4区 · 医学

Preventive and Therapeutic Efficacy of ONO-4641, a Selective Agonist for Sphingosine 1-Phosphate Receptor 1 and 5, in Preclinical Models of Type 1 Diabetes Mellitus

4区 · 医学

Article

作者: Shioya, Hiroki ; Kurata, Haruto ; Hiraizumi, Kenji ; Habashita, Hiromu ; Sato, Kazutoyo ; Inagaki, Yuichi ; Hoshino, Tomohiro ; Nakade, Shinji

ONO-4641, 1-({6-[(2-methoxy-4-propylbenzyl)oxy]-1-methyl-3,4-dihydronaphthalen-2-yl}methyl)azetidine-3-carboxylic acid (ceralifimod), is a second-generation sphingosine 1-phosphate receptor agonist selective for sphingosine 1-phosphate receptors 1 and 5, and has clinical effects in multiple sclerosis. The objective of the present study was to explore other potential indications for ONO-4641 based on its immunomodulatory effects. ONO-4641 was tested in non-obese diabetic (NOD) mice, an animal model of spontaneous type 1 diabetes mellitus, an autoimmune disease with unmet medical needs. ONO-4641 at a dose of 0.1 mg/kg prevented the onset of diabetes mellitus in NOD mice. Furthermore, ONO-4641 at doses of 0.03 and 0.1 mg/kg decreased diabetic prevalence in NOD mice after the onset of diabetes mellitus in a dose-dependent manner. Histopathological analysis demonstrated that insulin-positive areas in the islets of mice administered 0.03 and 0.1 mg/kg ONO-4641 showed a tendency of high values although they were not significantly different from the Control group, which was treated with vehicle. These observations suggest ONO-4641 may delay the onset and progression of type 1 diabetes mellitus.

2018-11-08·Journal of Medicinal Chemistry1区 · 医学

Where Do Recent Small Molecule Clinical Development Candidates Come From?

1区 · 医学

Review

作者: Brown, Dean G. ; Boström, Jonas

An analysis of 66 published clinical candidates from Journal of Medicinal Chemistry has been conducted to shed light on which lead generation strategies are most frequently employed in identifying drug candidates. The most frequent lead generation strategy (producing a drug candidate) was based on starting points derived from previously known compounds (43%) followed by random high throughput screening (29%). The remainder of approaches included focused screening, structure-based drug design (SBDD), fragment-based lead generation (FBLG), and DNA-encoded library screening (DEL). An analysis of physicochemical properties on the hit-to-clinical pairs shows an average increase in molecular weight (ΔMW = +85) but no change in lipophilicity (ΔclogP = -0.2), although exceptions are noted. The majority (>50%) of clinical candidates were found to be structurally very different from their starting point and were more complex. Finally, several reports of noncovalent scaffolds modified by a covalent warhead using SBDD approaches are discussed.

100 项与 Ceralifimod 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16123

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
复发-缓解型多发性硬化	临床2期	比利时	Ono Pharmaceutical Co., Ltd.	2010-10-01
复发-缓解型多发性硬化	临床2期	俄罗斯	Merck KGaA	2010-10-01
复发-缓解型多发性硬化	临床2期	德国	Ono Pharmaceutical Co., Ltd.	2010-10-01
复发-缓解型多发性硬化	临床2期	乌克兰	Ono Pharmaceutical Co., Ltd.	2010-10-01
复发-缓解型多发性硬化	临床2期	日本	Ono Pharmaceutical Co., Ltd.	2010-10-01
复发-缓解型多发性硬化	临床2期	美国	Merck KGaA	2010-10-01
复发-缓解型多发性硬化	临床2期	加拿大	Ono Pharmaceutical Co., Ltd.	2010-10-01
复发-缓解型多发性硬化	临床2期	希腊	Merck KGaA	2010-10-01
复发-缓解型多发性硬化	临床2期	捷克	Ono Pharmaceutical Co., Ltd.	2010-10-01
复发-缓解型多发性硬化	临床2期	波兰	Ono Pharmaceutical Co., Ltd.	2010-10-01

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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


NCT01226745 (DreaMS, CTgov)	临床2期	复发-缓解型多发性硬化	340	ONO-4641 (ONO-4641 0.10 mg - 0.10 mg)	鏇網膚齋餘餘憲夢鹹壓(構襯壓範壓廠蓋齋繭網) = 醖膚製願觸艱簾獵鑰鬱鹽襯範齋餘憲範壓蓋選 (鹹膚鏇遞積齋鬱膚醖鑰, 積壓願蓋鹹遞廠構鹹繭 ~ 鏇構蓋構蓋鹽鹹餘糧夢) 更多	-	2016-07-12
				ONO-4641 (ONO-4641 0.05 mg - 0.05 mg)	鏇網膚齋餘餘憲夢鹹壓(構襯壓範壓廠蓋齋繭網) = 醖襯繭範廠選鬱蓋願觸鹽襯範齋餘憲範壓蓋選 (鹹膚鏇遞積齋鬱膚醖鑰, 蓋襯簾簾醖鑰觸觸醖鬱 ~ 憲鏇蓋製鑰壓餘糧繭願) 更多
DreaMS study (ECTRIMS2013)	N/A	多发性硬化症	360	Placebo/0.05 mg ONO-4641	壓顧鑰網窪衊積築艱選(艱選網選窪範範蓋願衊) = 淵鹽構淵鏇鑰廠願簾窪簾壓製衊淵獵鹹製顧願 (網夢鏇憲醖餘繭網積衊 )	-	2013-09-30
				Placebo/0.10 mg ONO-4641	壓顧鑰網窪衊積築艱選(艱選網選窪範範蓋願衊) = 衊築鑰築夢艱衊鹹繭餘簾壓製衊淵獵鹹製顧願 (網夢鏇憲醖餘繭網積衊 )
DreaMS study (ECTRIMS2013)	N/A	多发性硬化症	343	ONO-4641 0.10mg	(繭顧衊夢積夢夢製觸觸): ARR = 0.16 (95% CI, 0.08 ~ 0.33), P-Value = 0.005	-	2013-09-30
				Placebo/ONO-4641 0.05mg
NCT01081782 (DreaMS, AAN2013)	临床2期	复发-缓解型多发性硬化	-	Placebo	(鏇壓蓋築壓製襯遞繭築) = 膚鬱鏇糧繭衊鬱廠選淵構鹹廠鏇餘築顧顧簾築 (製簾鑰窪淵顧築艱選糧 ) 更多	积极	2013-02-12
				ONO-4641 0.05 mg	(鏇壓蓋築壓製襯遞繭築) = 夢艱繭窪艱艱淵獵鹹壓構鹹廠鏇餘築顧顧簾築 (製簾鑰窪淵顧築艱選糧 ) 更多
NCT01081782 \| NCT01226745 (DreaMS, AAN2013)	临床2期	复发-缓解型多发性硬化	-	Placebo	獵醖艱鹹簾鏇觸範遞獵(醖觸鏇壓顧鏇艱製膚簾): relative reduction = 70 (95% CI, 54 ~ 81)	-	2013-02-12
				ONO-4641 0.05 mg