更新于：2024-11-01

TGM3

更新于：2024-11-01

基本信息

别名

Protein-glutamine gamma-glutamyltransferase E、Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain、Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chain

+ [8]

简介

Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity). In hair follicles, involved in cross-linking structural proteins to hardening the inner root sheath.

关联

项与 TGM3 相关的药物

CN116515786

专利挖掘

靶点

TGM3

作用机制-

在研机构

广东医科大学

原研机构

广东医科大学

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TGM3 相关的临床结果

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100 项与 TGM3 相关的转化医学

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0 项与 TGM3 相关的专利（医药）

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271

项与 TGM3 相关的文献（医药）

2024-08-01·Heliyon

Potential drug targets for osteoporosis identified: A Mendelian randomization study

Article

作者: Li, Zhong ; Wang, Qian ; Zhang, Kun ; Lu, Yao ; Zhao, Guolong ; Sun, Liang ; Duan, Ning

BackgroundOsteoporosis is a prevalent global health condition, primarily affecting the aging population, and several therapies for osteoporosis have been widely used. However, available drugs for osteoporosis are far from satisfactory because they cannot alleviate disease progression. This study aimed to explore potential drug targets for osteoporosis through Mendelian randomization analysis.MethodsUsing cis-expression quantitative trait loci (cis-eQTL) data of druggable genes and two genome-wide association studies (GWAS) datasets related to osteoporosis (UK Biobank and FinnGen cohorts), we employed mendelian randomization (MR) analysis to identify the druggable genes with causal relationships with osteoporosis. Subsequently, a series of follow-up analyses were conducted, such as colocalization analysis, cell-type specificity analysis, and correlation analysis with risk factors. The association between potential drug targets and osteoporosis was validated by qRT-PCR.ResultsSix druggable genes with causal relationships with osteoporosis were identified and successfully replicated, including ACPP, DNASE1L3, IL32, PPOX, ST6GAL1, and TGM3. Cell-type specificity analysis revealed that PPOX and ST6GAL1 were expressed in all cell types in the bone samples, while IL32, ACPP, DNASE1L3, and TGM3 were expressed in specific cell types. The GWAS data showed there were seven risk factors for osteoporosis, including vitamin D deficiency, COPD, physical activity, BMI, MMP-9, ALP and PTH. Furthermore, ACPP was associated with vitamin D deficiency and COPD; DNASE1L3 was linked to physical activity; IL32 correlated with BMI and MMP-9; and ST6GAL1 was related to ALP, physical activity, and MMP-9. Among these risk factors, only MMP-9 had a high genetic correlation with osteoporosis. The results of qRT-PCR demonstrated that IL32 was upregulated while ST6GAL1 was downregulated in peripheral blood of osteoporosis patients.ConclusionOur findings suggested that those six druggable genes offer potential drug targets for osteoporosis and require further clinical investigation, especially IL32 and ST6GAL1.

2024-08-01·Cell Reports

TGM1/3-mediated transamidation of Exo70 promotes tumor metastasis upon LKB1 inactivation

Article

作者: Shang, Jin ; Zhang, Haoran ; Deng, Yabin ; Chen, Xiong ; Xiong, Huifang ; Li, Guixia ; Chen, Lu ; Zhang, Wenqing ; Wang, Daxuan ; Hou, Jihuan ; Mei, Kunrong ; Zhan, Yan-Yan ; Gao, Yan ; Guo, Wei ; Liu, Di-Ao ; Hu, Tianhui ; Ke, Sunkui ; Hong, Xiaoting

Exo70, a key exocyst complex component, is crucial for cell motility and extracellular matrix (ECM) remodeling in cancer metastasis. Despite its potential as a drug target, Exo70's post-translational modifications (PTMs) are poorly characterized. Here, we report that Exo70 is transamidated on Gln5 with Lys56 of cystatin A by transglutaminases TGM1 and TGM3, promoting tumor metastasis. This modification enhances Exo70's association with other exocyst subunits, essential for secreting matrix metalloproteinases, forming invadopodia, and delivering integrins to the leading edge. Tumor suppressor liver kinase B1 (LKB1), whose inactivation accelerates metastasis, phosphorylates TGM1 and TGM3 at Thr386 and Thr282, respectively, to inhibit their interaction with Exo70 and the following transamidation. Cantharidin, a US Food and Drug Administration (FDA)-approved drug, inhibits Exo70 transamidation to restrain tumor cell migration and invasion. Together, our findings highlight Exo70 transamidation as a key molecular mechanism and target and propose cantharidin as a therapeutic strategy with direct clinical translational value for metastatic cancers, especially those with LKB1 loss.

2024-07-01·Microbial Pathogenesis

Study on the immune-enhancing and inhabiting transmissible gastroenteritis virus effects of polysaccharides from Cimicifuga rhizoma

Article

作者: Ma, Wuren ; Cui, Jing ; Fan, Yunpeng ; Wang, Xingchen ; Liu, Yingqiu ; Lu, Dezhang ; Zhang, Weimin ; Li, Huicong ; Tan, Xuewen ; Liu, Nishang

Cimicifugae rhizoma is a traditional Chinese herbal medicine in China, and modern pharmacological research showed that it has obvious antiviral activity. Many polysaccharides have been proved to have immune enhancement and antiviral activity, but there are few studies on the biological activity of Cimicifuga rhizoma polysaccharide (CRP). The aim was to explore the character of CRP and its effects on improving immune activity and inhibiting transmissible gastroenteritis virus (TGEV). The monosaccharide composition, molecular weight, fourier transform infrared spectra and electron microscopy analysis of CRP was measured. The effect of CRP on immune activity in lymphocytes and RAW264.7 cells were studied by colorimetry, FITC-OVA fluorescent staining and ELISA. The effect of CRP on TGEV-infected PK-15 cells was determined using Real-time PCR, Hoechst fluorescence staining, trypan blue staining, acridine orange staining, Annexin V-FITC/PI fluorescent staining, DCFH-DA loading probe, and JC-1 staining. Network pharmacology was used to predict the targets of CRP in enhancing immunity and anti-TGEV, and molecular docking was used to further analyze the binding mode between CPR and core targets. The results showed that CRP was mainly composed of glucose and galactose, and its molecular weight was 64.28 kDa. The content of iNOS and NO in CRP group were significantly higher than the control group. CRP (125 and 62.5 μg/mL) could significantly enhance the phagocytic capacity of RAW264.7 cells, and imprive the content of IL-1β content compared with control group. 250 μg/mL of CRP possessed the significant inhibitory effect on TGEV, which could significantly reduce the apoptosis compared to TGVE group and inhibit the decrease in mitochondrial membrane potential compared to TGVE group. The mRNA expression of TGEV N gene in CRP groups was significantly lower than TGEV group. PPI showed that the core targets of immune-enhancing were AKT1, MMP9, HSP90AA1, etc., and the core targets of TGE were CASP3, MMP9, EGFR, etc. Molecular docking show that CRP has binding potential with target. These results indicated that CRP possessed the better immune enhancement effect and anti-TGEV activity.

项与 TGM3 相关的新闻（医药）

2024-01-21

·药融圈

投资2.5亿！重庆普佑制药医药中间体及原料药（洛伐他汀、富马酸磷丙替诺福韦、辛伐他汀、替卡格雷、沙库巴曲缬沙坦钠等）

▲3月7-8日成都生物医药创新者峰会 · 点击立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。近日，关于重庆普佑制药有限公司医药中间体及原料药（一期）在相关网站公示。项目基本情况项目名称：医药中间体及原料药（一期）建设单位：重庆普佑制药有限公司建设地点：万州经济技术开发区九龙园龙翔北路建设性质：新建工程投资：25000万元，其中包括环保投资1000万元建设工期：2年占地面积和建筑面积：占地面积约211亩，一期工程建筑面积24671.94m2产品方案项目涉及11个医药中间体，建成后达到2275.51t/a的生产规模。备注：TA-2（（R）-（1-（6-氨基-9H-嘌呤-9-基）丙-2-基）氧基）甲基）膦酸，CAS：147127-20-6，用于生产富马酸磷丙替诺福韦）TAA-1（6-氨基-9-(2-丙酮基)嘌呤，CAS：105970-02-3，用于TAA生产）SV（辛伐他汀，CAS：79902-63-9）TAA（（R）-1-（6-氨基-9H-嘌呤-9-基）丙-2-醇，CAS：14047-28-0，用于TA-2生产）SV-2（（3R，5R）-3,5-二羟基-7-（（1S，2S，6R，8S）-8-羟基-2,6-二甲基-1,2,6,7,8,8-六氢萘-1-基）庚酸，CAS：132748-10-8，用于SV生产）TGM1-2（（（3aR，4R，6aR）-6-甲氧基-2,2-二甲基四氢呋喃[3,4-d][1,3]二氧基-4-基）甲醇，CAS：72402-14-3，用于TGM1-3生产）TGM1-3（（（3aR，4R，6aR）-6-甲氧基-2,2-二甲基四氢呋喃[3,4-d][1,3]二氧基-4-基）甲基-4-甲基苯磺酸酯，CAS：4137-56-8，用于TGM1-4生产）TGM1-4（（3aS，4S，6aR）-4-（碘甲基）-6-甲氧基-2,2-二甲基四氢呋喃[3,4-d][1,3]二噁戊烷，CAS：38838-06-1，用于TGM1-5生产）TGM1-11（2-(((3aS,4R,6S,6aR)-6-氨基-2,2-二甲基四氢-3HH-环戊二烯并[d][1,3]二氧杂环戊烯-4-基)氧基)乙醇(2S,3S)2,3-二羟基琥珀酸酯（简称：TGM1酒石酸盐），CAS：2376278-72-5，用于合成替卡格雷）TGM3-2（2-氯-1-（3,4-二氟苯基）乙烷-1-酮，CAS：51336-95-9，用于 TGM3-3 生产）SB-4（（R，E）-5-（[1，1'-联苯]-4-基）-4-（（叔丁氧基羰基）氨基）-2-甲基戊-2-烯酸乙酯，CAS：2131788-25-3，用于 SB-5 生产）SB-6（产品名称：4-（（（2S）-1-（[1，1'-联苯]-4-基）-5-乙氧基-4-甲基-5-氧代戊烷-2-基）氨基）-4-氧代丁酸，CAS：149709-62-6，用于合成沙库巴曲钠）重庆普佑制药有限公司成立于2022年11月，由南京鸿兴生物医药有限公司和几位自然人组建而成。坐落于万州经开区九龙园区，专门从事特色医药中间体的研发、生产与销售，并提供合同研发与合同生产服务。南京鸿兴生物医药有限公司专注于高端医药原料药和关键中间体研发、生产和销售。版权声明：本文转自原料药情报局，如不希望被转载的媒体或个人可与我们联系，我们将立即删除活动推荐 3月 • NDC x 2024新药创新者峰会关键词： ADC，改良型新药，小分子新药，GLP-1药物（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

申请上市

2022-10-30

·医药地理

精益求精 | 原料药“产业绿色发展”下的生存之道

10月30日，由中国医药工业研究总院、医药先进制造国家工程研究中心、创新药物与制药工艺国家重点实验室和中国医药工业信息中心共同主办，《中国医药工业杂志》承办的2022年中国医药工业大会暨《中国医药工业杂志》学术年会“原料药生物合成与绿色制药论坛”顺利召开，会议邀请了制药领域专家和研发精英共探绿色制药产业的健康发展之路。担任本场论坛主席的华东理工大学教授魏东芝以“生物催化、合成生物学与绿色生物制造”为主题分享了其团队的科研成果。酶分子机器与细胞工厂是生物质加工到生物基产品的关键所在，魏教授团队建立了自主酶库（含5000余种），依据酶的区域选择性与立体选择性，对酶进行靶向发掘，并借助计算机辅助，大幅缩短酶的底物筛选所消耗的时间。魏教授谈到，依靠酶与生物催化技术平台、细胞工厂与生物合成技术平台，可以生产药品、农药、高端化学品、食品、健康产品、环保产品等各门类的生物制造产品。海军军医大学药学系教授张卫东作了“基于中药的创新药物发现策略”的精彩分享。他提到，西方的药物研发模式是“以靶寻药”，即从靶点出发筛选化合物，然而这种模式的不确定性相当多，不仅研发周期长，失败风险也高。张教授表示，中药创新药物研究的关键科学问题是阐明中药药效物质基础与作用机制，即从有效的药物中寻找靶点既而研发新药。随后，张教授介绍了其团队如何基于临床疗效，采用化学生物学技术对中药鸦胆子抗肿瘤活性新机制进行发现、对新型构象锁定蜂毒肽及其溶瘤免疫作用机制进行研究的案例。中国医药工业研究总院研究员奕栋以“生物催化与生物合成技术创新与应用”为主题作了演讲。他指出，药物的生物催化合成技术难点涉及多学科的技术交叉融合。奕栋研究员阐述了系统生物催化技术的研究和发展现状，通过蛋白晶体结构解析、计算机结构模拟和定向进化技术改造野生型酶，使酶适合工业合成需要。随后，他对当前生物催化剂研究的五种技术，即生物合成路径设计、生物催化剂替代和迭代、超高通量筛选和进化、生物合成过程控制以及生物合成质量控制等进行了深入讲解，并提出了多技术融合化的发展建议。中国医药工业研究总院研究员冯军以“生物合成多肽类药物的研发进展及其案例分析”为主题作了报告。他首先介绍了多肽药物的定义、特点以及多肽药物的开发现状和未来的重点发展方向。随后，冯军研究员分享了其课题组对多黏菌素E甲磺酸钠的研究和产业化成果，多黏菌素E甲磺酸钠的物质基础异常复杂，组成成分多达近百个，因此被认为是迄今最复杂的抗生素之一。十几年来，冯军和他的团队直面困难、坚持研发，攻克了生产、分析、质控等相关的几十个技术难题，不断提升生产工艺和质量控制水平，为多黏菌素E甲磺酸钠的成功上市打下了坚实的药学研究基础。上海交通大学讲席教授朱建伟分享了“基因瞬时表达加速生物药物创新研发”的主题报告。他提到，在精准个性化的创新生物药物开发过程中会有相当多的药物被淘汰，因此，研发人员需要大量进行快速早期开发，在成功率在1%-5%的情况下，尽早筛选出有价值的、可以进一步进入临床开发的分子。然而，现有的生产工艺较难去除一些与抗体产品相关联、结构相类似的杂质，对临床效果会产生不利影响。他以IGFBP7、IL-7 TGE、Anti-PD1等三个实操案例来进一步说明如何利用生物合成技术平台优化药物分子表达式并进行纯化等工艺，从而生产出更稳定的、足够产量的生物药物。中国医药工业研究总院研究员陈少欣围绕“微生物药物工业生产菌种改造关键技术”的主题作了分享。他介绍到，开发自主核心酶和菌种是生物制造产业的“芯片”，微生物药物工业菌种的改造意义在于满足工业化生产要求。陈少欣与其研究团队在菌种库菌种筛选、菌种改造或从头构建上积累了一定的技术优势。他为与会者们分享了其研究团队利用CRISPR/Cas9基因编辑在工业丝状真菌上进行基因敲除、敲入和替换的应用，卡泊芬前体PB0及其类似物的分离纯化，米卡芬净前体FR901379生产菌基因编辑方法的建立，以及阿卡波糖菌种代谢工程的改造等成功经验。中国医药工业研究总院研究员李继安为与会者们带来了“微生物药物绿色制造工艺研发案例及思考”的专题报告。他阐述了微生物绿色制药的价值和工艺特点、难点，并结合具体案例分享了当前发酵物料分离纯化问题的应对策略。他指出，技术单元要尽可能互补，在工艺优化上要遵守“避免坏掉、减少跑掉”，“动工艺、不动设备”以及“变废为宝”几条原则。最后，李继安研究员以依替米星联产庆大霉素为案例，分享了如何实现依替米星国内首次结晶，庆大霉素生产过程中多余废弃组分Cla回收作为依替米星的合成原料，该工艺获得了2019年国家科技进步二等奖。本次论坛的上、下半场分别由中国医药工业研究总院研究员陈少欣和中国医药工业研究总院研究员奕栋主持。END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

微生物疗法