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-

登录后查看时间轴

结构

分子式C22H41O5P

InChIKeyPUPWWTUVIZOPTB-KTKRTIGZSA-N

CAS号633278-53-2

查看全部结构式(2)

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

登录后查看更多信息

100 项与 2ccPA 相关的转化医学

登录后查看更多信息

100 项与 2ccPA 相关的专利（医药）

登录后查看更多信息

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·Prostaglandins & Other Lipid Mediators

Effects of 2-carba-cyclic phosphatidic acid derivatives on IL-1β-stimulated human chondrocytes

Article

作者: Morohoshi, Toshiro ; Yoshii, Masaki ; Imamura, Shigeyuki ; Tsukahara, Tamotsu

Osteoarthritis (OA) is a common joint disease characterized by the breakdown of subchondral bone and cartilage damage, most often affecting middle-aged and elderly people. Although the etiology of OA is still unknown, some reports suggest that inflammatory factors such as interleukin (IL)- 1β mediate the progression of OA. To investigate the effect of IL-1β and the possibility of treatment for OA, we applied 2-carba-cyclic phosphatidic acid (2ccPA) and its derivatives on human chondrocytes. 2ccPA is a synthesized phospholipid derived from a bioactive phospholipid mediator: cyclic phosphatidic acid (cPA). It has been previously reported that 2ccPA exhibits anti-inflammatory and chondroprotective effects in an OA animal model. 2ccPA and its ring-opened body (ROB) derivative significantly suppressed IL-1β-induced upregulation of IL-6, matrix metalloproteinase-13, and cyclooxygenase-2, as well as the degradation of type II collagen and aggrecan. However, the other two derivatives, namely the deacylated and ring-opened deacylated bodies, showed little effect on an IL-1β-exposed human chondrosarcoma cell-line. These data suggest that the intactness of 2ccPA and ROB is essential for anti-inflammatory effects on OA. Collectively, this study provides evidence that 2ccPA and ROB would be novel therapeutic agents for OA.

100 项与 2ccPA 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

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