作者: Mao, Jia-Wen ; Xie, Can-Can ; Cheng, Meng-Nan ; Xiang, Mai ; Litifu, Dilinaer ; Lin, Ze-Min ; Zhu, Feng-Hua ; He, Yi-Fan ; Yao, Jia-Ying ; Xiong, Xiao-Yu ; Wu, Chun-Mei ; Zhu, Jin-Zhi ; He, Shi-Jun ; Yang, Xiao-Qian ; Zuo, Jian-Ping ; Tong, Xiao

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 μL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.

2024-01-01·Biomedicine & Pharmacotherapy

Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway

Article

作者: He, Shi-Jun ; Yang, Xiao-Qian ; Xiong, Xiao-Yu ; Chen, Li ; Yuan, Wen-Long ; Zhu, Feng-Hua ; Xiang, Mai ; Lin, Ze-Min ; Zuo, Jian-Ping ; Fan, Shu-Hui ; Chang, Yuan ; Cheng, Meng-Nan ; Wei, Wen-Hui

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin β3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention.

2021-02-01·International Immunopharmacology2区 · 医学

DZ2002 alleviates psoriasis-like skin lesions via differentially regulating methylation of GATA3 and LCN2 promoters

2区 · 医学

Article

作者: Zuo, Jianping ; Huang, Yueteng ; Yang, Xiaoqian ; Zhu, Fenghua ; Lin, Zemin ; Tang, Wei ; He, Shijun ; Liu, Yuting ; Cao, Shiqi ; Chen, Li

Psoriasis is the most prevalent inflammatory skin disorders, affecting 1-3% of the worldwide population. We previously reported that topical application of methyl 4-(adenin-9-yl)-2-hydroxybutanoate (DZ2002), a reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, was a viable treatment in murine psoriatic skin inflammation. In current study, we further explored the mechanisms of DZ2002 on keratinocyte dysfunction and skin infiltration, the key pathogenic events in psoriasis. We conducted genome-wide DNA methylation analysis in skin tissue from imiquimod (IMQ)-induced psoriatic and normal mice, demonstrated that topical administration of DZ2002 directly rectified aberrant DNA methylation pattern in epidermis and dermis of psoriatic skin lesion. Especially, DZ2002 differentially regulated DNA methylation of GATA3 and LCN2 promoters, which maintained keratinocytes differentiation and reduced inflammatory infiltration in psoriatic skin respectively. In vitro studies in TNF-α/IFN-γ-elicited HaCaT manifested that DZ2002 treatment rectified compromised keratinocyte differentiation via GATA3 enhancement and abated chemokine expression by reducing LCN2 production under inflammatory stimulation. Chemotaxis assays conducted on dHL-60 cells confirmed that suppression of LCN2 expression by DZ2002 was accompanied by CXCR1 and CXCR2 downregulation, and contributed to the inhibition of CXCL8-driven neutrophils migration. In conclusion, therapeutic benefits of DZ2002 are achieved through differentially regulating DNA methylation of GATA3 and LCN2 promoters in psoriatic skin lesion, which efficiently interrupt the pathogenic interplay between keratinocytes and infiltrating immune cells, thus maintains epidermal keratinocytes differentiation and prevents dermal immune infiltration in psoriatic skin.

项与脱氧菇嘌甲酯相关的新闻（医药）

2023-07-10

·信狐药迅

驯鹿 CAR-T伊基仑赛，豪森培莫沙肽，特宝拓培非格司亭获批上市 | 新获批（7.3-7.9）

每周药品注册受理数据，分门别类呈现，一目了然。（7.3-7.9）新药上市申请药品名称企业名称分类受理号伊基仑赛注射液南京驯鹿生物医药有限公司1CXSS2200055利拉鲁肽注射液杭州中美华东制药有限公司3.2CXSS22000643.2CXSS2200065培化西海马肽注射液江苏豪森药业集团有限公司1CXHS21010451CXHS21010441CXHS2101043培莫沙肽注射液1CXHS22000201CXHS22000211CXHS2200022拓培非格司亭注射液厦门特宝生物工程股份有限公司1CXSS22000451CXSS22000461CXSS22000471CXSS2200048注射用醋酸戈舍瑞林缓释微球山东绿叶制药有限公司2.2CXHS2101059赛帕利单抗注射液广州誉衡生物科技有限公司2.2CXSS2200025新药临床申请药品名称企业名称分类受理号DZ2002宁波紫园药业有限责任公司1CXHL23004411CXHL2300442FWD1802片深圳福沃药业有限公司1CXHL23004381CXHL23004391CXHL2300440HRS-9815注射液天津恒瑞医药有限公司1CXHL2300436HRS-9815注射液制备用药盒1CXHL2300437HS-10518胶囊江苏豪森药业集团有限公司1CXHL2300398IBI354信达生物制药(苏州)有限公司1CXSL2300303JMKX000197注射液浙江杭煜制药有限公司1CXHL23004561CXHL2300457JY016注射液北京东方百泰生物科技股份有限公司1CXSL2300295QL1706注射液齐鲁制药有限公司1CXSL2300305TQB3454片正大天晴药业集团股份有限公司1CXHL23004461CXHL2300448TST001注射液苏州创胜医药集团有限公司1CXSL2300302卟硒啉片上海元熙医药科技有限公司1CXHL23003951CXHL23003961CXHL2300397奥雷巴替尼片广州顺健生物医药科技有限公司2.4CXHL2300435布比卡因脂质体注射液江苏恒瑞医药股份有限公司2.4CXHL23004092.4CXHL23004102.4CXHL23004042.4CXHL2300405德谷门冬双胰岛素注射液重庆宸安生物制药有限公司3.3CXSL23003003.3CXSL2300301注射用SKB264四川科伦博泰生物医药股份有限公司1CXSL2300288注射用WXTJ0262辰欣药业股份有限公司1CXHL2300429注射用培重组人凝血因子IX-Fc融合蛋白郑州晟斯生物科技有限公司1CXSL23002601CXSL2300259注射用左亚叶酸上海汇伦医药股份有限公司2.4CXHL23004522.4CXHL2300453盐酸鲁拉西酮口溶膜四川科伦药业股份有限公司2.2CXHL2300411重组抗BCMA和CD3双特异性抗体注射液华兰基因工程(河南)有限公司1CXSL2300287仿制药申请药品名称企业名称分类受理号乙磺酸尼达尼布软胶囊齐鲁制药有限公司4CYHS22002794CYHS2200280他克莫司软膏山东良福制药有限公司4CYHS2101409山东达因海洋生物制药股份有限公司4CYHS2101408利伐沙班片宁波科尔康美诺华药业有限公司4CYHS22002654CYHS22002664CYHS2101631利多卡因丙胺卡因气雾剂则正(上海)生物科技有限公司3CYHL2300063匹伐他汀钙片石家庄四药有限公司4CYHS21017074CYHS2101706卡培他滨片上海上药信谊药厂有限公司4CYHS2102135卡贝缩宫素注射液海南皇隆制药股份有限公司4CYHS2101993右佐匹克隆片常州四药制药有限公司3CYHS2200427吸入用盐酸丙卡特罗溶液南京华盖制药有限公司3CYHS2102099呋塞米注射液吉林振澳制药有限公司3CYHS2102082复方醋酸钠电解质注射液华仁药业股份有限公司3CYHS1700015头孢羟氨苄干混悬剂上海金城素智药业有限公司3CYHS21010383CYHS2101037奥氮平盐酸氟西汀胶囊江苏长泰药业股份有限公司3CYHS22007063CYHS22007073CYHS22007083CYHS22007093CYHS2200710奥美沙坦酯氨氯地平片江苏万高药业股份有限公司4CYHS2200144奥美沙坦酯片重庆医药(集团)股份有限公司4CYHS2101831左氧氟沙星片上海金城素智药业有限公司4CYHS21012834CYHS2101282帕拉米韦注射液扬子江药业集团有限公司3CYHS2100136恩格列净片乐普药业股份有限公司4CYHS21018784CYHS2101879托吡司特片国药集团容生制药有限公司3CYHL23000653CYHL2300066拉莫三嗪缓释片上海奥科达医药科技股份有限公司3CYHS2201288普瑞巴林口服溶液合肥恩瑞特药业有限公司3CYHS2101844济川药业集团有限公司3CYHS2100143来曲唑片海南日中天制药有限公司4CYHS2102268枸橼酸西地那非口崩片河北龙海药业有限公司4CYHS2200018枸橼酸西地那非片广州白云山光华制药股份有限公司4CYHS21023144CYHS21023154CYHS2102313核黄素磷酸钠滴眼液宁夏康亚药业股份有限公司3CYHS2201261氧(液态)谷城宏泰气体有限公司4CYHS2200498氨磺必利片山东京卫制药有限公司4CYHS21017034CYHS2101704泊沙康唑注射液齐鲁制药(海南)有限公司4CYHS2101699注射用头孢美唑钠/氯化钠注射液湖南科伦制药有限公司3CYHS2102231注射用头孢西丁钠/氯化钠注射液北京锐业制药有限公司3CYHS22003353CYHS2200336洛匹那韦利托那韦片上海迪赛诺医药集团股份有限公司4CYHS2200484洛索洛芬钠凝胶膏北京茗泽中和药物研究有限公司4CYHL2300064玻璃酸钠滴眼液湖北远大天天明制药有限公司4CYHS2200271琥珀酸去甲文拉法辛缓释片石药集团欧意药业有限公司3CYHS2200192甲硫酸新斯的明注射液成都苑东生物制药股份有限公司3CYHS22000983CYHS2200099盐酸右美托咪定氯化钠注射液四川国瑞药业有限责任公司3CYHS2102064盐酸奥普力农注射液国药集团容生制药有限公司3CYHS2200464盐酸普拉克索缓释片北京北陆药业股份有限公司4CYHS21016744CYHS2101673盐酸氟西汀口服液安徽新世纪药业有限公司3CYHS2101369盐酸氨溴索氯化钠注射液陕西金裕制药股份有限公司6CYHS1301433盐酸美金刚口服溶液合肥科大生物技术有限公司3CYHS2201406盐酸羟甲唑啉滴眼液南京恒道医药科技股份有限公司3CYHL2300059盐酸艾司洛尔注射液北京新美泰克医药科技有限公司3CYHS2102258盐酸莫西沙星滴眼液石家庄凯赛医药科技有限公司4CYHS2101957广州大光制药有限公司4CYHS2101805盐酸西那卡塞片博瑞制药(苏州)有限公司4CYHS2200322盐酸阿罗洛尔片成都苑东生物制药股份有限公司4CYHS2102130硫辛酸注射液福安药业集团烟台只楚药业有限公司4CYHS2102123硫酸氢氯吡格雷片广东东阳光药业有限公司4CYHS1900577磷酸奥司他韦胶囊江苏迪赛诺制药有限公司4CYHS2102144珠海同源药业有限公司4CYHS2101678磷酸西格列汀片惠升生物制药股份有限公司4CYHS21022894CYHS2102290北京元延医药科技股份有限公司4CYHS21021134CYHS2102112磺达肝癸钠注射液博瑞制药(苏州)有限公司4CYHS2200201索磷布韦片乳源东阳光药业有限公司4CYHS2101941羧甲司坦口服溶液广东华南药业集团有限公司3CYHS2200152聚乙烯醇滴眼液中山万汉制药有限公司4CYHS17003164CYHS1700062蒙脱石散河南羚锐制药股份有限公司4CYHS2101797酒石酸美托洛尔片浙江京新药业股份有限公司4CYHS2200005阿卡波糖片北京京丰制药集团有限公司4CYHS2102219阿哌沙班片合肥英太制药有限公司4CYHS2101308阿普米司特片江苏正大清江制药有限公司4CYHS21020384CYHS21020394CYHS2102040阿瑞匹坦胶囊江苏海岸药业有限公司4CYHS21020554CYHS2102054非布司他片浙江诺得药业有限公司4CYHS22000214CYHS2200022宜昌人福药业有限责任公司4CYHS2102239进口申请药品名称企业名称分类受理号ARV-471(PF-07850327)片Pfizer Inc.1JXHL2300095BAY 1747846 注射液Bayer AG1JXHL2300086BBP-398胶囊LianBio Development (HK) Limited1JXHL23001011JXHL2300102BLU-5937片Bellus Health Cough Inc.1JXHL23000961JXHL2300097Mim8Novo Nordisk A/S1JXSL23000861JXSL23000871JXSL23000881JXSL23000891JXSL2300090RO7434656注射液F. Hoffmann-La Roche Ltd.1JXHL2300098乌帕替尼缓释片AbbVie Deutschland GmbH & Co.KG2.4JXHS22000952.4JXHS22000972.4JXHS2200096富马酸喹硫平片阿拉宾度制药有限公司5.2JXHS19001855.2JXHS19001865.2JXHS19001875.2JXHS1900188富马酸福莫特罗吸入溶液Mylan Specialty LP5.1JXHS2101034拉米地坦片Eli Lilly and Company5.1JXHS2200018氮卓斯汀氟替卡松鼻用喷雾剂天津开心生活科技有限公司5.1JXHS2000162注射用SAR444200Sanofi-Aventis Recherche & Developpement1JXSL2300081注射用英夫利西单抗CELLTRION, Inc.3.3JXSS2100022注射用阿扎胞苷杭州泰格医药科技股份有限公司5.2JXHS1900102盐酸帕罗西汀片阿拉宾度制药有限公司5.2JYHS21000545.2JYHS21000535.2JYHS21000525.2JYHS2100051盐酸替洛利生薄膜衣片Bioprojet Pharma5.1JXHS21010505.1JXHS2101049盐酸纳呋拉啡口崩片Toray Industries, Inc.5.1JXHS2101099硝苯地平控释片Elite Pharmaceutical Solution, Inc.5.2JYHS2200027硫酸吗啡缓释胶囊Mayne Pharma International Pty Ltd.5.1JXHL23000895.1JXHL23000905.1JXHL23000915.1JXHL2300092艾加莫德α注射液argenx BV3.1JXSS2200022中药相关申请药品名称企业名称分类受理号HYZ2001胶囊天地恒一制药股份有限公司1.1CXZL2300030养阴舒肝颗粒广州医药研究总院有限公司1.1CXZL2300027脑心清片广州白云山和记黄埔中药有限公司2.3CXZL2300029注：灰色字体部分结论为不批准或收到通知件；不包含原料药、医用氧、注射用水、氯化钠或葡萄糖注射液等申请，不包含再注册、一次性进口、技术转移、复审申请。

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100 项与脱氧菇嘌甲酯相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
银屑病	临床1期	中国	宁波紫园药业有限责任公司	2024-03-04
系统性红斑狼疮	药物发现	中国	中国科学院上海药物研究所	2017-03-30
系统性红斑狼疮	药物发现	中国	宁波紫园药业有限责任公司	2017-03-30