Delving into the Latest Updates on Sansho Co., Ltd. with Synapse

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疾病领域	数量

免疫系统疾病	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

LPAR x autotaxin	1

关联

1

项与 Sansho Co., Ltd. 相关的药物

2ccPA

靶点

LPAR x autotaxin

作用机制

LPAR激动剂 [+1]

在研机构

Tokyo Women's Medical University Educational Association [+2]

原研机构

SANSHO Co. Ltd. (Tokyo) [+2]

在研适应症

膝关节炎 [+2]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期-

100 项与 Sansho Co., Ltd. 相关的临床结果

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0 项与 Sansho Co., Ltd. 相关的专利（医药）

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43

项与 Sansho Co., Ltd. 相关的文献（医药）

2022-01-01·Proceedings for Annual Meeting of The Japanese Pharmacological Society

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

作者: Masaki, Yoshii ; Tsukahara, Tamotsu ; Morobosi, Toshirou

2014-09-01·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts

Article

作者: Gotoh, Mari ; Murakami-Murofushi, Kimiko ; Maeda-Sano, Katsura ; Morohoshi, Toshiro ; Someya, Takao ; Murofushi, Hiromu

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway.

2014-01-01·Molecular Pain3区 · 医学

Cyclic Phosphatidic Acid Relieves Osteoarthritis Symptoms

3区 · 医学

ArticleOA

作者: Morohoshi, Toshiro ; Gotoh, Mari ; Nagano, Aya ; Tsukahara, Ryoko ; Otsuka, Kazuyuki ; Murakami-Murofushi, Kimiko ; Murofushi, Hiromu

Background: Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. Natural cPA and its chemically stabilized cPA derivative, 2-carba-cPA (2ccPA), inhibit chronic and acute inflammation, and 2ccPA attenuates neuropathic pain. Osteoarthritis (OA) is a degenerative disease frequently associated with symptoms such as inflammation and joint pain. Because 2ccPA has obvious antinociceptive activity, we hypothesized that 2ccPA might relieve the pain caused by OA. We aimed to characterize the effects of 2ccPA on the pathogenesis of OA induced by total meniscectomy in the rabbit knee joint. Results: Intra-articular injection of 2ccPA (twice a week for 42 days) significantly reduced pain and articular swelling. Histopathology showed that 2ccPA suppressed cartilage degeneration in OA. We also examined the effects of 2ccPA on the inflammatory and catabolic responses of human OA synoviocytes and chondrosarcoma SW1353 cells in vitro. 2ccPA stimulated synthesis of hyaluronic acid and suppressed production of the metalloproteinases MMP-1, −3, and −13. However, it had no effect on the production of interleukin (IL)-6, an inflammatory cytokine. The suppressive effect of 2ccPA on MMP-1 and −3 production in synoviocytes and on MMP-13 production in SW1353 cells was not mediated by the lysophosphatidic acid receptor, LPA1 receptor (LPA1R). Conclusions: Our results suggest that 2ccPA significantly reduces the pain response to OA by inducing hyaluronic acid production and suppressing MMP-1, −3, and −13 production in synoviocytes and chondrocytes.

100 项与 Sansho Co., Ltd. 相关的药物交易

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100 项与 Sansho Co., Ltd. 相关的转化医学

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