2ccPA(2ccPA) - 药物靶点：LPAR x autotaxin_在研适应症：膝关节炎，骨关节炎，类风湿关节炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

2-Carba cyclic phosphatidic acid

靶点

LPAR x autotaxin

作用机制

LPAR激动剂(溶血磷脂酸受体激动剂)、autotaxin抑制剂(核苷酸内焦磷酸酶/磷酸二酯酶2抑制剂)

治疗领域

免疫系统疾病皮肤和肌肉骨骼疾病

在研适应症

膝关节炎骨关节炎类风湿关节炎

非在研适应症-

原研机构

SANSHO Co. Ltd. (Tokyo)

友华生技医药股份有限公司Tokyo Women's Medical University

在研机构

Tokyo Women's Medical University Educational Association

Sansho Co., Ltd.

友华生技医药股份有限公司

非在研机构-

最高研发阶段临床1/2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

分子式C22H41O5P

InChIKeyPUPWWTUVIZOPTB-KTKRTIGZSA-N

CAS号633278-53-2

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关联

2

项与 2ccPA 相关的临床试验

NCT05807529 / Active, not recruiting临床1/2期

A Phase I-II, Dose-escalation, Double-blinded, Placebo-controlled, and Dose-finding Study to Evaluate the Safety and Efficacy of 2ccPA in Patients With Osteoarthritis of the Knee

This phase I/II study aims to evaluate the safety of single doses of 2ccPA 4,800 μg and 7,200 μg (Phase I), as well as the safety and efficacy of multiple doses of 2ccPA (Phase II) in patients with osteoarthritis (OA) of the knee.

开始日期2022-11-03

申办/合作机构

友华生技医药股份有限公司

NCT04229394 / Completed临床1期

Phase I Safety, Tolerability, and Pharmacokinetics Study of 2ccPA in Patients With Symptomatic Knee Osteoarthritis

This clinical trial is designed to determine safety and tolerability as well as the MTD of a single-dose 2ccPA and PK data in symptomatic knee OA.

开始日期2018-02-13

申办/合作机构

友华生技医药股份有限公司

100 项与 2ccPA 相关的临床结果

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100 项与 2ccPA 相关的转化医学

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100 项与 2ccPA 相关的专利（医药）

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20

项与 2ccPA 相关的文献（医药）

2023-11-01·Brain Research

2-Carba cyclic phosphatidic acid regulates blood coagulation and fibrinolysis system for repair after brain injury

Article

作者: Miyamoto, Yasunori ; Gotoh, Mari ; Murakami-Murofushi, Kimiko ; Kawamoto, Yuka ; Hashimoto, Kei ; Nakashima, Mari ; Sakai, Shiho ; Endo, Misaki

Effective blood coagulation prevents inflammation and neuronal loss after brain injury. 2-Carba-cyclic phosphatidic acid (2ccPA), a biotherapeutic for brain injury, inhibits blood extravasation resulting from blood-brain barrier breakdown. However, the hemostasis mechanism of 2ccPA remains unclear. We determined the effects of 2ccPA-injection on blood coagulation and fibrinolysis using a needle-induced brain injury model. 2ccPA suppressed the expression of platelet degranulation-related genes. Immediately after brain injury, 2ccPA increased CD41⁺ platelet aggregation around the lesions and promoted fibrin aggregation. Additionally, 2ccPA supported fibrinolysis by upregulating plasminogen activator expression. These results suggest the acute effects of 2ccPA on brain hemostasis.

2023-11-01·Human cell

Two-carba cyclic phosphatidic acid treatment promotes phenotypic switch from M1 to M2 microglia and prevents behavioral abnormalities in a mouse model of neuropsychiatric systemic lupus erythematosus.

Article

作者: Gotoh, Mari ; Fukasawa, Keiko ; Ishizuka, Toshiaki ; Koizumi, Akiho ; Nagata, Wataru ; Satoh, Yasushi ; Nakagawa, Keiichi

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the production of double-stranded DNA (dsDNA) antibodies and other antibodies that predominantly affects women with a wide range of lesions. Although neuropsychiatric lupus erythematosus (NPSLE), characterized by neuropsychiatric symptoms related to cerebrovascular diseases or depression, ranks high in severity, no specific treatment has been defined. Two-carba cyclic phosphatidic acid (2ccPA), a derivative of cyclic phosphatidic acid, was isolated from the true slime mold Physarum polycephalum in 1992. 2ccPA treatment suppresses neuroinflammation and promotes tissue repair in mouse multiple sclerosis and traumatic brain injury models. In this study, we performed behavioral tests on MRL/lpr mice as an NPSLE model. MRL/lpr mice showed increased depression-like behaviors compared with control mice, which were significantly suppressed by 2ccPA treatment. The expression of CD68, an M1 phenotypic marker of microglia, was significantly elevated in the prefrontal cortex and hippocampus of MRL/lpr mice, which was significantly suppressed by 2ccPA treatment. In contrast, the expression of Arginase1, an M2 phenotypic marker of microglia, was significantly increased by 2ccPA treatment. Compared to control mice, MRL/lpr mice showed higher plasma levels of anti-dsDNA antibodies, which are mainly involved in SLE pathogenesis. 2ccPA treatment decreased these levels in the MRL/lpr mice. These results suggest that 2ccPA treatment suppresses behavioral abnormalities by promoting a microglial phenotypic switch from M1 to M2 in MRL/lpr mice.

2023-02-01·Neuroscience Letters

2-carba-cyclic phosphatidic acid modulates astrocyte-to-microglia communication and influences microglial polarization towards an anti-inflammatory phenotype

Article

作者: Gotoh, Mari ; Miyamoto, Yasunori ; Takei, Rino ; Endo, Misaki ; Hashimoto, Kei ; Murakami-Murofushi, Kimiko ; Nakashima, Mari

2-carba-cyclic phosphatidic acid (2ccPA) suppresses microglial and astrocyte inflammation for neuronal survival following traumatic brain injury. However, it remains unknown how 2ccPA regulates microglial activation. In this study, to elucidate the 2ccPA behavior in glial communication, we collected the astrocyte conditioned media (ACM) from primary astrocyte cultures that were treated by lipopolysaccharide (LPS) and 2ccPA and analyzed the alteration of microglial inflammation caused by the ACM treatment. The addition of the ACM derived from LPS- and 2ccPA-double treated astrocytes to microglia decreased the CD86⁺ pro-inflammatory M1 microglia, which were upregulated with the ACM collected from astrocytes treated by LPS without 2ccPA, while the direct addition of LPS and 2ccPA to microglia failed to decrease the CD86⁺ microglia to the basal level. We confirmed that the ACM from LPS- and 2ccPA-treated astrocytes increased the ratio of CD206⁺ anti-inflammatory M2 microglia to total microglia, whereas direct treatment of microglia with LPS and 2ccPA had no effect on the CD206⁺ microglia ratio, demonstrating the importance of astrocyte intervention in microglial polarization. In addition, we examined whether astrocytes modulate the 2ccPA-regulated proinflammatory cytokine production derived from microglia. The addition of the ACM from LPS- and 2ccPA-treated astrocytes to microglia remarkably canceled the LPS-induced upregulation of IL-1β, IL-6, and TNF-α secreted from microglia, while the direct addition of LPS and 2ccPA to microglia showed no affect. Therefore, our results indicate that astrocytes mediate the 2ccPA function to shift microglia towards the M2 phenotype by interfering with the polarization of M1 microglia and to suppress cytokine production.

100 项与 2ccPA 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
膝关节炎	临床2期	中国台湾	友华生技医药股份有限公司	2022-11-03
骨关节炎	临床前	日本	Tokyo Women's Medical University Educational Association	2017-06-14
骨关节炎	临床前	日本	Sansho Co., Ltd.	2017-06-14
类风湿关节炎	临床前	日本	Sansho Co., Ltd.	2017-06-14
类风湿关节炎	临床前	日本	Tokyo Women's Medical University Educational Association	2017-06-14