Folia Pharmacologica Japonica最新文献_第4页

[Pharmacological characteristics and clinical study results of danicopan (Voydeya^® tablets)]. 【达尼可泮（Voydeya®片）的药理特性及临床研究结果】。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25017

Hideo Hayashi

{"title":"[Pharmacological characteristics and clinical study results of danicopan (Voydeya® tablets)].","authors":"Hideo Hayashi","doi":"10.1254/fpj.25017","DOIUrl":"10.1254/fpj.25017","url":null,"abstract":"Danicopan (brand name: Voydeya® tablets) is a new oral small molecule complement factor D inhibitor that was approved in Japan in January 2024 for paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare, chronic hematologic disorder caused by acquired mutations of hematopoietic stem cells in the PIGA gene. These mutations cause deficiencies in complement regulatory proteins CD55 and CD59 that may lead to uncontrolled terminal complement activation, intravascular hemolysis, thrombosis, and premature mortality. Complement C5 inhibitors (C5i; eculizumab and ravulizumab) are the current standard of care of PNH treatment, and control intravascular hemolysis (IVH) by inhibiting terminal complement pathway activation. However, extravascular hemolysis (EVH) with persistent symptoms, such as anemia, occurs in some C5i-treated patients with PNH. EVH is caused by the accumulation of proximal complement C3 fragment on the membrane of surviving PNH-type red blood cells. These cells subsequently undergo phagocytosis in the spleen or liver. Danicopan was developed to control EVH by targeting complement factor D involved in alternative pathway activation. Preclinical studies showed that danicopan selectively inhibits alternative complement pathway activation by reversibly binding to factor D and inhibiting its serine protease activity. A global phase III study (ALPHA study: ALXN2040-PNH-301 [NCT04469465]) investigated danicopan as add-on therapy to ravulizumab or eculizumab in patients with PNH and clinically significant EVH. Danicopan achieved statistically significant, clinically meaningful increases in hemoglobin levels, reduced transfusion, and reduced fatigue, while maintaining control of IVH. No new safety concerns were observed. Danicopan makes it possible to control EVH while controlling IVH with C5i.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"279-290"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24095

Hiroko Makihara

引用次数: 0

[Mechanisms of allergen-specific immunotherapy]. [过敏原特异性免疫治疗机制]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24084

Hideaki Morita

{"title":"[Mechanisms of allergen-specific immunotherapy].","authors":"Hideaki Morita","doi":"10.1254/fpj.24084","DOIUrl":"https://doi.org/10.1254/fpj.24084","url":null,"abstract":"Allergen-specific immunotherapy (AIT) has been a longstanding treatment for allergic diseases. Historically, subcutaneous immunotherapy was the main approach, but with the development of sublingual preparations, which are associated with fewer systemic side effects, sublingual immunotherapy is gaining global popularity. In Japan, the approval of standardized sublingual immunotherapy preparations in 2014 has significantly accelerated its adoption. The mechanism of allergic inflammation is divided into sensitization and elicitation phases. The sensitization phase involves the production of antigen-specific IgE antibodies against a particular antigen. These IgE antibodies bind to FcεRI on mast cells and basophils, preparing the body for an allergic response. The elicitation phase occurs when the body, already primed with these antibodies, is re-exposed to the same antigen, triggering inflammation and symptoms. This phase includes mechanisms where IgE-mediated mast cell activation leads to degranulation and where local Th2 cell activation induces inflammation. While the mechanisms of AIT are not fully understood, they are categorized into desensitization and immune tolerance. Desensitization is induced by reducing the responsiveness of mast cells and basophils to the antigen. Immune tolerance involves the production of antigen-specific IgG4 antibodies that compete with IgE for antigen binding, and the induction of regulatory T cells and other anti-inflammatory immune cells producing cytokines such as IL-10. AIT still faces challenges, such as the lack of predictive biomarkers for efficacy. Recent studies indicate that HLA genotypes influence AIT responsiveness. Advances in genetic and single-cell analysis are expected to address these challenges, paving the way for improved treatment outcomes.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 1","pages":"43-47"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Preface]. (前言)。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24096

Takeshi Nabe

引用次数: 0

[Mechanism of transduction of itch and strategy of treatment for itch]. [痒的传导机制和治疗痒的策略]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24080

Kenji Izuhara, Satoshi Nunomura, Yasuhiro Nanri, Yuko Honda

{"title":"[Mechanism of transduction of itch and strategy of treatment for itch].","authors":"Kenji Izuhara, Satoshi Nunomura, Yasuhiro Nanri, Yuko Honda","doi":"10.1254/fpj.24080","DOIUrl":"10.1254/fpj.24080","url":null,"abstract":"Itch is an unpleasant sense to evoke desire to scratch skin. Itch not only disturbs daily lives, but also exacerbates inflammation in case of atopic dermatitis (AD). It had been thought that both itch and pain are transduced by the same neurons; however, it is now known that neutrons transducing either itch or pain are distinct. Moreover, TRP channels, a family of calcium channels, play an important role for transducing itch as well as pain, temperature, and pressure. Development of neuroscience and molecular biology has dramatically advanced our understanding of how itch is transduced in recent years. On the other hand, development of immunology has revealed that there exist several immune types in our host defense mechanism and that type 2 immune reaction is dominant in the pathogenesis of allergic diseases including AD. Although it had been already known that type 2 cytokines contribute to the pathogenesis of AD by binding to their receptors on both immune cells and tissue resident cells, it has been recently found that several type 2 cytokines directly transduce the itch signals by binding to peripheral nerves. Due to this discovery, we can understand more deeply the itch mechanism of AD and can develop molecularly targeted drugs for AD targeting type 2 cytokines, which has dramatically changed the treatment of AD. In this review article, we describe the progress of our recent understanding of the itch mechanism and the strategy of treatment against it.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"79-85"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[The potential of BCL6B as a therapeutic target for chorioretinal vascular lesions]. BCL6B作为绒毛膜视网膜血管病变治疗靶点的潜力。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24064

Shinsuke Nakamura, Hideaki Hara

引用次数: 0

[The 77th Regional Meeting (Seinan Area)]. [第77届区域会议（塞南地区）]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.S24105

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25003

Shigeo Miyata

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[Preface]. (前言)。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24079

Youichi Shinozaki, Shinsuke Nakamura

引用次数: 0

[Pharmacological properties and clinical trial results of the novel calcium-sensing receptor agonist upacicalcet sodium hydrate (Upacita^® intravenous injection for dialysis)]. 【新型钙敏感受体激动剂upacicalcet sodium hydrate （Upacita®透析静脉注射）的药理学特性及临床试验结果】。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24108

Takeju Otsuki, Seigo Akari, Naomi Kashiwagi, Yoshiyuki Ono

{"title":"[Pharmacological properties and clinical trial results of the novel calcium-sensing receptor agonist upacicalcet sodium hydrate (Upacita® intravenous injection for dialysis)].","authors":"Takeju Otsuki, Seigo Akari, Naomi Kashiwagi, Yoshiyuki Ono","doi":"10.1254/fpj.24108","DOIUrl":"https://doi.org/10.1254/fpj.24108","url":null,"abstract":"Upacicalcet sodium hydrate (upacicalcet) is a novel small-molecule calcium-sensing receptor (CaSR) modulator with an amino acid structure, developed in Japan as a derivative from research into taste enhancement. Upacicalcet specifically targets CaSR and is thought to inhibit parathyroid hormone (PTH) secretion by activating the receptor in the presence of extracellular calcium (Ca). In nonclinical studies, upacicalcet was evaluated for its pharmacological properties, binding characteristics, and effects on ectopic calcification, parathyroid hyperplasia, and bone disorders associated with secondary hyperparathyroidism (SHPT). The results supported its mechanisms of action, binding mode, and efficacy in suppressing disease progression. In clinical trials, upacicalcet demonstrated efficacy and safety in patients with SHPT undergoing hemodialysis, as assessed in domestic Phase I/II trial (AJ1001 trial), Phase II trial (AJ1002 trial), Phase III placebo-controlled trial (AJ1004 trial), and Phase III long-term administration trial (AJ1003 trial). Upacicalcet was approved in June 2021 for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing hemodialysis and was launched in August of the same year.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"207-219"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0