Delving into the Latest Updates on 2ccPA with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-Carba cyclic phosphatidic acid

Target

LPAR x autotaxin

Action

agonists, inhibitors

Mechanism

LPAR agonists(Lysophosphatidic acid receptors agonists), autotaxin inhibitors(Ectonucleotide pyrophosphatase/phosphodiesterase 2 inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication

Osteoarthritis, KneeOsteoarthritisRheumatoid Arthritis

Inactive Indication-

Originator Organization

SANSHO Co. Ltd. (Tokyo)

Orient Europharma Co. Ltd.Tokyo Women's Medical University

Active Organization

Tokyo Women's Medical University Educational Association

Orient Europharma Co. Ltd.

Sansho Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H41O5P

InChIKeyPUPWWTUVIZOPTB-KTKRTIGZSA-N

CAS Registry633278-53-2

View All Structures (2)

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.

01 Nov 2023·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

Author: 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.

01 Feb 2023·Prostaglandins & Other Lipid Mediators

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

Article

Author: 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 Deals associated with 2ccPA

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis, Knee	Phase 2	Taiwan Province	Orient Europharma Co. Ltd.	03 Nov 2022
Osteoarthritis	Preclinical	Japan	Tokyo Women's Medical University Educational Association	14 Jun 2017
Osteoarthritis	Preclinical	Japan	Sansho Co., Ltd.	14 Jun 2017
Rheumatoid Arthritis	Preclinical	Japan	Sansho Co., Ltd.	14 Jun 2017
Rheumatoid Arthritis	Preclinical	Japan	Tokyo Women's Medical University Educational Association	14 Jun 2017