A Gram-stain-negative, strictly aerobic and oval-shaped bacterial strain with a flagellum, designated GS-10T, was isolated from mangrove wetland sediment. GS-10T grew at 20–40 °C (optimum, 37 °C), in the pH range of 5.0–11.0 (optimum, 6.0–8.0) and under various NaCl concentrations from 1 to 11 % (w/v) (optimum, 5–6 %). The respiratory quinone was ubiquinone-10, and the predominant polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The major fatty acids (>10 % of the total fatty acids) were summed feature 4 (C17 : 1iso I/anteiso B) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The G+C content of the genomic DNA was 63.71 %. On the basis of the results from comparative analysis of the 16S rRNA gene sequence, GS-10T represents a member of the family

Rhodobacteraceae

and had the highest sequence similarity to

Thalassobius gelatinovorus

CECT 4357T (97.47 %), followed by

Lutimaribacter pacificus

W11-2BT (97.03 %),

Marivita cryptomonadis

CL-SK44T (96.83 %),

Thalassobius autumnalis

CECT 5118T (96.75 %) and

Thalassobius mediterraneus

CECT 5383T (96.68 %). Phylogenetic trees based on 16S rRNA gene sequences, multilocus sequence analysis (MLSA) and whole genome sequences revealed that GS-10T clustered with species within the genus

Thalassobius

. The average nucleotide identity (ANI) and the average amino acid identity (AAI) values were calculated from complete genome sequences and indicated that GS-10T represented a novel species of the genus

Thalassobius

, and the name Thalassobius mangrovi sp. nov. is proposed for this species. The type strain of Thalassobius mangrovi is GS-10T (=MCCC 1K03624T=KCTC 82131T).

2017-04-01·Medical Microbiology and Immunology4区 · 医学

iTRAQ-based quantitative proteomics reveals important host factors involved in the high pathogenicity of the H5N1 avian influenza virus in mice

4区 · 医学

Article

作者: Gu, Min ; Liu, Xiufan ; Hu, Jiao ; Liang, Yanyan ; Liu, Wenbo ; Liu, Huimou ; Liu, Xiaowen ; Gao, Zhao ; Wang, Xiaoquan ; Hu, Shunlin ; Chen, Sujuan ; Peng, Daxin

We previously reported a pair of H5N1 avian influenza viruses which are genetically similar but differ greatly in their virulence in mice. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly lethal to mice, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is avirulent. In this study, to investigate the host factors that account for their virulence discrepancy, we compared the pathology and host proteome of the CK10- or GS10-infected mouse lung. Moderate lung injury was observed from CK10-infected animals as early as the first day of infection, and the pathology steadily progressed at later time point. However, only mild lesions were observed in GS10-infected mouse lung at the late infection stage. Using the quantitative iTRAQ coupled LC-MS/MS method, we first found that more significantly differentially expressed (DE) proteins were stimulated by GS10 compared with CK10. However, bio-function analysis of the DE proteins suggested that CK10 induced much stronger inflammatory response-related functions than GS10. Canonical pathway analysis also demonstrated that CK10 highly activated the "Acute Phase Response Signaling," which results in a wide range of biological activities in response to viral infection, including many inflammatory processes. Further in-depth analysis showed that CK10 exacerbated acute lung injury-associated responses, including inflammatory response, cell death, reactive oxygen species production and complement response. In addition, some of these identified proteins that associated with the lung injury were further confirmed to be regulated in vitro. Therefore, our findings suggest that the early increased lung injury-associated host response induced by CK10 may contribute to the lung pathology and the high virulence of this virus in mice.

2014-05-01·Biochimica et Biophysica Acta (BBA) - Biomembranes

Structure–activity relationships of the antimicrobial peptide gramicidin S and its analogs: Aqueous solubility, self-association, conformation, antimicrobial activity and interaction with model lipid membranes

Article

作者: Prenner, Elmar J ; Mant, Colin T ; Lewis, Ruthven N A H ; Keller, Sandro ; Hodges, Robert S ; Abraham, Thomas ; McElhaney, Ronald N

GS10 [cyclo-(VKLdYPVKLdYP)] is a synthetic analog of the naturally occurring antimicrobial peptide gramicidin (GS) in which the two positively charged ornithine (Orn) residues are replaced by two positively charged lysine (Lys) residues and the two less polar aromatic phenylalanine (Phe) residues are replaced by the more polar tyrosine (Tyr) residues. In this study, we examine the effects of these seemingly conservative modifications to the parent GS molecule on the physical properties of the peptide, and on its interactions with lipid bilayer model and biological membranes, by a variety of biophysical techniques. We show that although GS10 retains the largely β-sheet conformation characteristic of GS, it is less structured in both water and membrane-mimetic solvents. GS10 is also more water soluble and less hydrophobic than GS, as predicted, and also exhibits a reduced tendency for self-association in aqueous solution. Surprisingly, GS10 associates more strongly with zwitterionic and anionic phospholipid bilayer model membranes than does GS, despite its greater water solubility, and the presence of anionic phospholipids and cholesterol (Chol) modestly reduces the association of both GS10 and GS to these model membranes. The strong partitioning of both peptides into lipid bilayers is driven by a large favorable entropy change opposed by a much smaller unfavorable enthalpy change. However, GS10 is also less potent than GS at inducing inverted cubic phases in phospholipid bilayer model membranes and at inhibiting the growth of the cell wall-less bacterium Acholeplasma laidlawii B. These results are discussed in terms of the comparative antibiotic and hemolytic activities of these peptides.

项与 GS10 相关的新闻（医药）

2022-08-17

·泽璟制药

泽璟制药第二个双功能抗体ZGGS18临床试验申请获得国家药监局批准

近日，泽璟制药收到国家药品监督管理局核准签发的《药物临床试验批准通知书》，公司自主研发的注射用ZGGS18（VEGF/TGF-β）用于治疗晚期实体瘤的临床试验获得批准。根据公开数据查询，目前暂无相同作用机制的药品在国内外获批上市或进入临床研究。这是继ZG005（PD-1/TIGIT）后，泽璟制药第二个获国家药监局批准开展临床试验的双特异性抗体类药物。此前，ZGGS18、ZG005用于治疗实体瘤的临床试验申请均已获得美国FDA批准，实现中美双报，标志着公司的新型抗体研发平台逐步步入收获期。 ZGGS18、ZG005有望成为治疗实体瘤的肿瘤免疫创新型生物制品，丰富泽璟制药分子靶向和肿瘤免疫双管齐下的肿瘤药产品管线。在生物医药领域，肿瘤免疫和分子靶向联合治疗已经显示出突出的治疗效果，将是未来肿瘤治疗的重要趋势。ZGGS18、ZG005和公司小分子靶向新药等具有联合协同增效作用，将能增强公司在肿瘤治疗领域的竞争优势。关于ZGGS18 ZGGS18是公司及子公司Gensun Biopharma Inc.通过双/多特异性抗体研发平台开发的一个双功能抗体融合蛋白药物，也是公司递交临床试验申请的第二个双特异性抗体类药物。ZGGS18的注册分类为治疗用生物制品1类，有望成为治疗实体瘤的创新型生物制品。 ZGGS18是一种重组人源化抗VEGF/TGF-β的双功能抗体融合蛋白，可以特异性地结合血管内皮生长因子（VEGF）和“捕获”转化生长因子-β（TGFβ），起到抑制肿瘤新生血管形成和降低肿瘤转移发生等协同抑制肿瘤生长的多重作用。另外，ZGGS18也可以改善和调节肿瘤微环境，从而可以和抗PD-1/L1抗体、公司正在开展临床研究的抗PD-1/TIGIT双特异性抗体ZG005等肿瘤免疫治疗药物联合增强肿瘤杀伤作用。临床前研究结果显示，ZGGS18在人非小细胞肺癌、结直肠癌等模型上具有显著的肿瘤抑制作用，且在和抗PD-1抗体联合治疗后，可以导致显著比例的小鼠肿瘤完全消退，说明ZGGS18具有强效的肿瘤杀伤作用和增强肿瘤免疫治疗药物疗效的潜力。ZGGS18在非人灵长类动物中显示出长半衰期等优良的药代动力学特征及良好的安全性特征。关于子公司GENSUN 子公司GENSUN（Gensun Biopharma Inc.）致力于发现和开发新型抗体。GENSUN拥有三个候选药物研发平台TriGen、CheckGen和TGen。TriGen平台为三特异抗体研发平台，可以突破抗体两个Fab段的限制，赋予分子结合三个不同靶点的能力。CheckGen平台可以产生以免疫检查点为靶点的双特异抗体候选新药。TGen平台为新型双特异抗体分子开发平台，所产生的候选药物分子可以用作单一药物治疗，可以彼此组合联合用药，也可以与抗PD1/PD-L1治疗药物组合。 GENSUN的产品线包括GS01、GS02、GS10、GS11、GS12、GS14、GS15、GS17、GS18、GS19等10余个在研项目。GENSUN累计申请专利40项，共获授权8项。GENSUN授予齐鲁制药GS02（针对TIGIT靶点）大中华地区的专利独家授权，授予开拓药业GS19（PD-L1/TGF-beta）在大中华区的专利独家授权。内容来源于网络，如有侵权，请联系删除。

抗体临床获批

2022-07-26

·药创客

泽璟制药第二个双功能抗体ZGGS18临床试验申请获得FDA批准

近日，泽璟制药在研产品 ZGGS18临床试验申请获得美国食品药品监督管理局（以下简称“FDA”）批准，用于治疗晚期实体瘤，这是公司获得FDA临床试验批准的第二个双特异性抗体类药物。 ZGGS18用于治疗晚期实体瘤的临床试验申请已经获得国家药品监督管理局受理，在中国的注册分类为治疗用生物制品1类，目前在国家药品监督管理局药品审评中心（CDE）的技术审评阶段。根据公开数据查询，目前暂无相同作用机制的药品在国内外获批上市或进入临床研究。关于ZGGS18 ZGGS18是公司及子公司Gensun Biopharma Inc.通过双/多特异性抗体研发平台联合开发的一个全新双功能抗体融合蛋白药物，也是公司获得FDA临床试验批准的第二个双特异性抗体类药物，有望成为治疗晚期实体瘤的创新型生物制品。 ZGGS18是一种重组人源化抗VEGF/TGF-β的双功能抗体融合蛋白，可以特异性地结合血管内皮生长因子（VEGF）和“捕获”转化生长因子-β（TGF-β），起到抑制肿瘤新生血管形成和降低肿瘤转移发生等协同抑制肿瘤生长的多重作用。另外，ZGGS18也可以改善和调节肿瘤微环境，从而可以和抗PD-1/L1抗体、公司正在开展临床研究的抗PD-1/TIGIT双特异性抗体ZG005等肿瘤免疫治疗药物联合增强肿瘤杀伤作用。临床前研究结果显示，ZGGS18在人非小细胞肺癌、结直肠癌等模型上具有显著的肿瘤抑制作用，且在和抗PD-1抗体联合用药后，可以导致显著比例的小鼠肿瘤完全消退，说明ZGGS18具有强效的肿瘤杀伤作用和增强肿瘤免疫治疗药物疗效的潜力。ZGGS18在非人灵长类动物中显示出长半衰期等优良的药代动力学特征及良好的安全性特征。关于子公司GENSUN 子公司GENSUN（Gensun Biopharma Inc.）致力于发现和开发新型抗体。GENSUN拥有三个候选药物研发平台TriGen、CheckGen和TGen。TriGen平台为三特异抗体研发平台，可以突破抗体两个Fab段的限制，赋予分子结合三个不同靶点的能力。CheckGen平台可以产生以免疫检查点为靶点的双特异抗体候选新药。TGen平台为新型双特异抗体分子开发平台，所产生的候选药物分子可以用作单一药物治疗，可以彼此组合联合用药，也可以与抗PD1/PD-L1治疗药物组合。 GENSUN的产品线包括GS01、GS02、GS10、GS11、GS12、GS14、GS15、GS17、GS18、GS19等10余个在研项目。GENSUN累计申请专利40项，共获授权8项。GENSUN授予齐鲁制药GS02（针对TIGIT靶点）大中华地区的专利独家授权，授予开拓药业GS19（PD-L1/TGF-beta）在大中华区的专利独家授权。

抗体临床获批

2022-07-25

·泽璟制药

喜讯 I 泽璟制药第二个双功能抗体ZGGS18临床试验申请获得FDA批准

NEWS 近日，泽璟制药在研产品 ZGGS18临床试验申请获得美国食品药品监督管理局（以下简称“FDA”）批准，用于治疗晚期实体瘤，这是公司获得FDA临床试验批准的第二个双特异性抗体类药物。ZGGS18用于治疗晚期实体瘤的临床试验申请已经获得国家药品监督管理局受理，在中国的注册分类为治疗用生物制品1类，目前在国家药品监督管理局药品审评中心（CDE）的技术审评阶段。根据公开数据查询，目前暂无相同作用机制的药品在国内外获批上市或进入临床研究。关于ZGGS18 ZGGS18是公司及子公司Gensun Biopharma Inc.通过双/多特异性抗体研发平台联合开发的一个全新双功能抗体融合蛋白药物，也是公司获得FDA临床试验批准的第二个双特异性抗体类药物，有望成为治疗晚期实体瘤的创新型生物制品。ZGGS18是一种重组人源化抗VEGF/TGF-β的双功能抗体融合蛋白，可以特异性地结合血管内皮生长因子（VEGF）和“捕获”转化生长因子-β（TGF-β），起到抑制肿瘤新生血管形成和降低肿瘤转移发生等协同抑制肿瘤生长的多重作用。另外，ZGGS18也可以改善和调节肿瘤微环境，从而可以和抗PD-1/L1抗体、公司正在开展临床研究的抗PD-1/TIGIT双特异性抗体ZG005等肿瘤免疫治疗药物联合增强肿瘤杀伤作用。临床前研究结果显示，ZGGS18在人非小细胞肺癌、结直肠癌等模型上具有显著的肿瘤抑制作用，且在和抗PD-1抗体联合用药后，可以导致显著比例的小鼠肿瘤完全消退，说明ZGGS18具有强效的肿瘤杀伤作用和增强肿瘤免疫治疗药物疗效的潜力。ZGGS18在非人灵长类动物中显示出长半衰期等优良的药代动力学特征及良好的安全性特征。关于子公司GENSUN 子公司GENSUN（Gensun Biopharma Inc.）致力于发现和开发新型抗体。GENSUN拥有三个候选药物研发平台TriGen、CheckGen和TGen。TriGen平台为三特异抗体研发平台，可以突破抗体两个Fab段的限制，赋予分子结合三个不同靶点的能力。CheckGen平台可以产生以免疫检查点为靶点的双特异抗体候选新药。TGen平台为新型双特异抗体分子开发平台，所产生的候选药物分子可以用作单一药物治疗，可以彼此组合联合用药，也可以与抗PD1/PD-L1治疗药物组合。GENSUN的产品线包括GS01、GS02、GS10、GS11、GS12、GS14、GS15、GS17、GS18、GS19等10余个在研项目。GENSUN累计申请专利40项，共获授权8项。GENSUN授予齐鲁制药GS02（针对TIGIT靶点）大中华地区的专利独家授权，授予开拓药业GS19（PD-L1/TGF-beta）在大中华区的专利独家授权。关于泽璟制药（688266.SH）泽璟制药（688266.SH）是一家专注于肿瘤、出血及血液疾病、免疫炎症性疾病和肝胆疾病等多个治疗领域的创新驱动型化学及生物新药研发和生产企业，是中国首家以科创板第五套标准上市的企业。公司建立了三个研发中心，分别位于江苏昆山、上海张江、美国加州，开发了丰富的小分子新药与大分子新药的产品管线，覆盖肝癌、非小细胞肺癌、结直肠癌、甲状腺癌、鼻咽癌、骨髓增殖性疾病等多种癌症和血液肿瘤以及出血、肝胆疾病、免疫炎症性疾病等多个治疗领域。公司注重同时布局大病种疾病和罕见病、广谱性和特效性，注重实现在研药品领先性和可及性，从而形成产品管线的差异化综合竞争优势。目前，公司在研16个新药的45项研发项目，子公司GENSUN的产品线包括10余个候选抗体新药。公司先后承担了５项国家“重大新药创制”、多项江苏省级科技项目；截至2022年3月31日，公司拥有已授权发明专利105项（含子公司GENSUN 8项）；公司累计申请发明专利253项（含子公司GENSUN 40项）。泽璟制药将始终致力于研发和生产具有全球自主知识产权、安全、有效、患者可负担的创新药物，以满足国内外巨大的临床需求。

抗体小分子药物免疫疗法

100 项与 GS10 相关的药物交易

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