更新于：2024-05-01

LCAT

磷脂酰胆碱-甾醇-酰基转移酶

更新于：2024-05-01

基本信息

别名

1-alkyl-2-acetylglycerophosphocholine esterase、LCAT、Lecithin-cholesterol acyltransferase

+ [5]

简介

Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs) (PubMed:10329423, PubMed:19065001, PubMed:26195816). The cholesterol ester is then transported back to the liver. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines (PubMed:8820107). Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms (PubMed:10722751). Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:8016111). Also catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF (PubMed:8016111). Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C monoesters (PubMed:24620755).

关联

项与 LCAT 相关的药物

MEDI-6012

靶点

LCAT

作用机制

LCAT调节剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 LCAT 相关的临床试验

NCT03773172 / Terminated临床2期

Study to Evaluate the Effects of Two Doses Over 48 Hours of MEDI6012 on Apolipoprotein B100 Metabolism in Subjects With Stable Atherosclerotic Cardiovascular Disease

This is a Phase 2, single-center, placebo controlled, double-blind, randomized crossover study to determine the effects of MEDI6012 on the metabolism of apolipoprotein B100 (apoB100) lipoproteins in individuals with stable atherosclerotic cardiovascular disease (ASCVD).

开始日期2019-01-31

申办/合作机构

Columbia University

[+2]

NCT03578809 / Completed临床2期

A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction

This is a Phase 2b randomized, blinded, placebo controlled study to evaluate the efficacy, safety, PK/pharmacodynamic, and immunogenicity of repeat doses of MEDI6012 in adult participants presenting with acute STEMI (ST segment elevation myocardial infarction).
The study will enrol participants presenting with acute STEMI who are planned for primary percutaneous coronary intervention (pPCI). For all participants, an end of study CMR will be performed at 10-12 weeks (70-84 days following Dose 1). A subset of participants will also undergo an index and an end of study CTA.

开始日期2018-06-05

申办/合作机构

MedImmune LLC

[+1]

EUCTR2017-004521-32-CZ / Not yet recruiting临床2期

A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction - REAL-TIMI 63B

开始日期2018-05-15

申办/合作机构-

100 项与 LCAT 相关的临床结果

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100 项与 LCAT 相关的转化医学

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0 项与 LCAT 相关的专利（医药）

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2,922

项与 LCAT 相关的文献（医药）

2024-01-09·Cancer cell international

Disulfidptosis-related signature predicts prognosis and characterizes the immune microenvironment in hepatocellular carcinoma.

Article

作者: Jun Tang ; Xintong Peng ; Desheng Xiao ; Shuang Liu ; Yongguang Tao ; Long Shu

BACKGROUND:

Disulfidptosis is a type of programmed cell death caused by excessive cysteine-induced disulfide bond denaturation leading to actin collapse. Liver cancer has a poor prognosis and requires more effective intervention strategies. Currently, the prognostic and therapeutic value of disulfidptosis in liver cancer is not clear.

METHODS:

We investigated the features of 16 disulfidptosis-related genes (DRGs) of HCC patients in the TCGA and classified the patients into two disulfidptosis pattern clusters by consensus clustering analysis. Then, we constructed a prognostic model using LASSO Cox regression. Next, the microenvironment and drug sensitivity were evaluated. Finally, we used qPCR and functional analysis to verify the reliability of hub DRGs.

RESULTS:

Most of the DRGs showed significantly higher expression in cancer tissues than in adjacent tissues. Our prognostic model, the DRG score, can well predict the survival of HCC patients. There were significant differences in survival, features of the microenvironment, effects of immunotherapy, and drug sensitivity between the high- and low-DRG score groups. Ultimately, we demonstrated that a few hub DRGs have differential mRNA expression between liver cancer cells and normal cells and that the protective gene LCAT can inhibit liver cancer metastasis in vitro.

CONCLUSION:

We established a novel risk model based on DRG scores to predict HCC patient prognosis, drug sensitivity and immunotherapy efficacy, which provides new insight into the relationship between disulfidptosis and HCC and provides valuable assistance for the personalized treatment of HCC.

2024-01-08·Discover. Oncology

A novel cholesterol metabolism-related ferroptosis pathway in hepatocellular carcinoma.

Article

作者: Weiwei Fang ; Jianyong Liu ; Fanguo Zhang ; Cheng Pang ; Xiying Li

BACKGROUND:

Emerging studies have reported the contribution of cholesterol to hepatocellular carcinoma (HCC) progression. However, the specific role and mechanism of cholesterol metabolism on spontaneous and progressive HCC development from the point of view of ferroptosis are still worth exploring. The present study aimed to reveal a novel mechanism of cholesterol metabolism-related ferroptosis in hepatocellular carcinoma cells.

METHODS:

Two microarray datasets (GSE25097, GSE22058) related to HCC were downloaded from Gene Expression Omnibus (GEO) datasets. Metabolomics analysis was performed by ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). The cholesterol-related proteins were downloaded from HMBD. Ferroptosis-related genes were extracted from FerrDb database. Data sets were separated into two groups. GSE25097 was used to identify ferroptosis-related genes, and GSE22058 was used to verify results. During these processes, chemical-protein interaction (CPI), protein-protein interaction (PPI), the Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Multivariate logistic regression analysis was used to test the associated pathway.

RESULTS:

We identified 8 differentially expressed ferroptosis-related genes (HAMP, PTGS2, IL1B, ALOX15B, CDKN2A, RRM2, NQO1 and KIF20A) and 4 differentially expressed cholesterol-related genes (LCAT, CH25H, CEL and CYP7A1). Furthermore, based on the predicted results with STITCH, we identified indomethacin and IL1B as the essential node for cholesterol-mediated ferroptosis in hepatocellular carcinoma cell. Multivariate logistic regression analysis showed the activities of plasma IL1B in liver cancer patients enrolled have been significantly affected by the level of plasma cholesterol (P < 0.001) and the test result of IL1B is a predictor variable causing the changes of serum Fe levels (P < 0.001).

CONCLUSIONS:

Our findings shed new light on the association between cholesterol metabolism and ferroptosis in HCC, and suggest that IL1B is the necessary node for cholesterol to lead to ferroptosis process in HCC. Also, we identified the potential role of indomethacin in adjuvant therapy of HCC with complications of abnormal cholesterol metabolism.

2024-01-08·Animals : an open access journal from MDPI

Effects of Thyroid Powder on Tadpole (Lithobates catesbeiana) Metamorphosis and Growth: The Role of Lipid Metabolism and Gut Microbiota.

Article

作者: Bo Zhu ; Chuang Shao ; Wenjie Xu ; Jihong Dai ; Guihong Fu ; Yi Hu

A low metamorphosis rate of amphibian larvae, commonly known as tadpoles, limits the farming production of bullfrogs (Lithobates catesbeiana). This study aimed to examine the effects of processed thyroid powder as a feed additive on tadpole metamorphosis, lipid metabolism, and gut microbiota. Five groups of tadpoles were fed with diets containing 0 g/kg (TH0), 1.5 g/kg (TH1.5), 3 g/kg (TH3), 4.5 g/kg (TH4.5), and 6 g/kg (TH6) thyroid powder for 70 days. The results showed that TH increased the average weight of tadpoles during metamorphosis, with the TH6 group having the highest values. The TH4.5 group had the highest metamorphosis rate (p < 0.05). Biochemical tests and Oil Red O staining showed that the lipid (triglyceride) content in the liver decreased after TH supplementation, especially at doses higher than 1.5 g/kg. RT-qPCR revealed that TH at doses higher than 4.5 g/kg significantly up-regulated the transcriptional expression of the pparα, accb, fas, fadd6, acadl, and lcat genes, which are related to lipid metabolism (p < 0.05). These results showed that TH seems to simultaneously promote the synthesis and decomposition of lipid and fatty acids, but ultimately show a decrease in lipids. As for the gut microbiota, it is noteworthy that Verrucomicrobia increased significantly in the TH4.5 and TH6 groups, and the Akkermansia (classified as Verrucomicrobia) was the corresponding genus, which is related to lipid metabolism. Specifically, the metabolic pathways of the gut microbiota were mainly enriched in metabolic-related functions (such as lipid metabolism), and there were significant differences in metabolic and immune pathways between the TH4.5 and TH0 groups (p < 0.05). In summary, TH may enhance lipid metabolism by modulating the gut microbiota (especially Akkermansia), thereby promoting the growth of tadpoles. Consequently, a supplementation of 4.5 g/kg or 6 g/kg of TH is recommended for promoting the metamorphosis and growth of tadpoles.

项与 LCAT 相关的新闻（医药）

2024-02-15

·BioSpace

ABIONYX Pharma Acknowledges the Clinical Results of the Phase 3 AEGIS-II Study Evaluating the Efficacy and Safety of CSL Behring’s Human-plasma-derived apoA-I, CSL112

TOULOUSE, France & LAKELAND, Mich.--(BUSINESS WIRE)-- Access here the full press release ABIONYX Pharma, (FR0012616852 – ABNX – PEA PME eligible), a new generation biotech company dedicated to the discovery and development of innovative therapies based on the world’s only natural recombinant apoA-I, today acknowledges that the Phase 3 AEGIS-II study evaluating the efficacy and safety of CSL Behring’s human-plasma-derived apoA-I, CSL112, compared to placebo in reducing the risk of major adverse cardiovascular events (MACE) in patients following an acute myocardial infarction (AMI), did not meet its primary efficacy endpoint of MACE reduction at 90 days. About CER-001 CER-001 is a novel engineered recombinant human apoA-I that was designed to mimic the structural and functional biological properties of natural, nascent HDL, also known as pre-β HDL, and has been shown to perform all steps of the Reverse Lipid Transport pathway (RLT), the only natural pathway responsible for lipid elimination. Administered CER-001 particles increase transient apoA-I and the number of HDL particles and promote the elimination of trapped cholesterol and lipids in tissues in the absence of LCAT enzyme for example, but also the elimination of bacterial lipid endotoxin (LPS) in the case of sepsis. HDL particles are then recognized by the liver, leading to the elimination of these transported lipids via a process called Reverse Lipid Transport (RLT). About ABIONYX Pharma ABIONYX Pharma is a next-generation biotech company focused on developing innovative medicines in diseases where there is no effective or existing treatment, even the rarest ones. The company expedites the development of novel therapeutics through an extensive expertise in lipid science and a differentiated apoA-I -based technology platform. ABIONYX Pharma is committed to radically improving treatment outcomes in sepsis and critical care. View source version on businesswire.com: Contacts NewCap Investor relations Nicolas Fossiez Louis-Victor Delouvrier abionyx@newcap.eu +33 (0)1 44 71 98 53 NewCap Media relations Arthur Rouillé abionyx@newcap.eu +33 (0)1 44 71 00 15 Source: ABIONYX Pharma View this news release online at:

临床3期临床结果

2023-06-19

·创鉴汇

13家创新药公司获融资！超8亿元助力眼病基因疗法新锐；科笛集团登陆港交所 | 融资周报

▎药明康德内容团队编辑据创鉴汇不完全统计，上周（6月12日至6月18日）全球大健康领域共披露融资事件29起。按照融资轮次划分，除未知轮外，早期融资（B轮以前）14起，中后期融资（B轮及以后）9起。融资所涉及的药物类型包括基因疗法、小分子靶向药、微生物组疗法、噬菌体疗法等。#019600万英镑助力新一代基因疗法开发，新锐剑指多种致盲性眼病关键词：基因疗法最新融资：9600万英镑未知轮本轮投资机构：OSE、Syncona Limited6月12日，Beacon Therapeutics宣布完成9600万英镑（约合8.8亿元）融资，本轮融资资金将用于推进研发针对视网膜疾病的新一代基因疗法。Beacon Therapeutics成立于2023年，致力于恢复和改善视网膜疾病患者的视力。其主要临床资产AGTC-501是一个正在进行2期临床试验的基因治疗项目，主要针对晚期X连锁视网膜色素变性（XLRP）疾病。AGTC-501的优势在于，它能正确表达全长的RPGR蛋白，从而解决XLRP引发的全部光感受器损伤问题，包括视杆细胞和视锥细胞的损伤。为了进一步完善其未来的产品管线，公司还成功引进了一项靶点生成技术平台，该平台将用于在眼科领域内识别、筛选和研究分泌蛋白。#02科笛集团在港交所正式上市关键词：小分子靶向药、酶最新融资：约3.93亿港元IPO6月12日，科笛集团在港交所正式上市。科笛集团成立于2019年，致力于开发全面的解决方案，以满足患者及消费者在广泛皮肤病治疗及护理市场中不断变化的多样化需求。成立以来，该公司已建立广泛的产品组合，涵盖获得性重组突变胶原酶CU-20401、特异性II型5α-还原酶竞争抑制剂CU-40102等9种候选产品，针对局部脂肪堆积管理、毛发疾病及护理、皮肤疾病及护理、表皮麻醉四个主要领域。目前，科笛集团正在开发5种临床阶段及4种临床前阶段候选药物，其中2款产品已在海南乐城开始商业化试点。#03诚益生物获1.8亿元B轮融资，推进小分子GLP-1受体激动剂等开发关键词：GLP-1受体激动剂最新融资：1.8亿元B轮本轮投资机构：元禾原点、兰石资本、华金投资、康禧全球投资基金、张科禾润、御富投资、清松资本、联新资本、骊宸投资6月12日，诚益生物（Eccogene）宣布获得1.8亿元人民币B轮融资。诚益生物是一家临床阶段的生物医药公司，其研发方向聚焦于代谢和免疫相关疾病。该公司旨在以疾病生物学、药物化学及临床转化医学为基础，以新颖视角建立的新颖和差异化的研发管线项目解决未满足的临床需求。据新闻稿，本轮融资所得将用于支持该公司临床阶段代谢管线的研发，包括治疗肥胖和2型糖尿病的小分子GLP-1受体激动剂ECC5004，以及用于非酒精性脂肪性肝炎（NASH）和脂质紊乱的THRβ完全激动剂ECC4703，并进一步推进诚益生物在代谢和免疫疾病方面的临床前项目研发。#04Feldan Therapeutics获1650万美元B轮融资，建设基于多肽的细胞内递送平台关键词：多肽最新融资：1650万美元B轮本轮投资机构：Amgen Ventures、FSIT2、GC Cell、GC Holdings、Investissement Quebec6月13日，Feldan Therapeutics宣布完成1650万美元B轮融资。该公司致力于研发细胞内递送技术，其基于多肽的技术平台Feldan Shuttle能够在细胞内递送多种化合物，针对尚未开发的细胞内治疗靶点。目前，Feldan公司的药物管线主要是针对皮肤病和肺部疾病，其主要候选产品FLD-103拟治疗基底细胞癌（BCC）。本轮资金将推进FLD-103的1/2期临床试验，并将针对肺部疾病的管线推进到临床前阶段。#05锦篮基因完成近亿元pre-B轮融资，推进腺相关病毒基因疗法临床研发关键词：基因疗法最新融资：近亿元pre-B轮本轮投资机构：乾道基金、东方富海6月16日，锦篮基因宣布完成近亿元pre-B轮融资。锦篮基因以腺相关病毒（AAV）载体递送技术介导的基因治疗药物开发为核心业务，专注于遗传性神经肌肉疾病、遗传代谢疾病、溶酶体疾病以及眼科疾病等领域的基因治疗药物开发。据悉，公司已有脊髓性肌萎缩症（SMA）基因治疗药物、高甘油三酯血症基因治疗药物、庞贝病基因治疗药物、家族性LCAT缺乏症基因治疗药物在内的多条基因治疗药物研发管线。本轮融资资金将用于提升AAV制品生产规模和商业化能力，支持锦篮基因新药产品注册上市。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。读者们请星标⭐创鉴汇，第一时间收到我们的推送更多数据内容推荐点击“在看”，分享创鉴汇健康新动态

基因疗法IPO临床2期临床1期

2023-06-16

·E药经理人

“一母同胞”的Biotech和CDMO战略重组，分分合合透露了什么信号?

“一母同胞”的锦篮基因与五加和基因完成战略重组合并了。今日（6月16日），锦篮基因宣布实现对五加和基因的战略重组合并，并完成近亿元Pre-B轮融资，由乾道基金领投，老股东东方富海持续加持。本轮融资将用于提升AAV制品生产规模和商业化能力，支持锦篮基因新药产品注册上市。公开资料显示，两家公司成立于2018年，锦篮基因专注于基因疗法新药研发，五加和基因专注于基因疗法CDMO服务。早有渊源虽然锦篮基因与五加和基因两家公司成立时间不算太久，但他们的缘分得从2005年说起。彼时，北京五加和分子医学研究所有限公司 (后文简称“五加和分子”) 成立，创始人为董小岩和吴小兵。两人属于国内较早一批专注于AAV载体基因药物相关技术的研发人员。其中吴小兵为国内第一个申请临床的AAV基因治疗药品的首席科学家。成立五加和分子后，两人又于2014年创建北京瑞希罕见病基因治疗技术研究所，先后开展了MPSIIIA、SMA、Pompe、X-ALD、GM1、MPSII 等罕见病的在模型动物体内的实验研究。这为锦篮基因与五加和基因的成立提供了“粮草”。四年后即2018年，五加和分子又成立了两家子公司。一是五加合基因科技有限公司（简称“五加合基因”），主攻病毒载体、基因药物的CDMO服务，为pre-IND和IND 阶段基因药物提供符合GMP标准的病毒载体制品研发生产服务等；核心技术和团队源于董小岩和吴小兵此前在任过的中国预防医学科学院病毒学研究所，病毒基因工程国家重点实验室。二是成立锦篮基因，主攻遗传性神经肌肉疾病、遗传代谢疾病、溶酶体疾病以及眼科疾病等领域基因治疗药物开发，以将基因治疗技术及产品从罕见病过渡到慢性病和其它重大疾病的治疗和康复。董小岩曾在一档医药行业直播中回忆称，“这 2 家公司是独立的，业务、团队、知识产权人员、投资人等完全分开了。为何在这时“分拆”？从另一创始人吴小兵公开发言或可见一斑，“融资”是其中一个较大原因。她曾提及，为了让北京瑞希罕见病基因治疗技术研究所的罕见病基因治疗项目获得融资，她于 2018年牵头成立锦篮基因。与此同时,该研究所治疗脊髓性肌萎缩症和庞贝病的2个AAV基因药物转入锦篮基因，以获得融资开发。两家子公司成立后，很快展开了各自融资之旅。锦篮基因分别在2021年2月、2022年2月完成了近亿元的天使轮融资、2亿元人民币A轮融资，以向前推进旗下基因治疗项目；而五加和基因也于2021年9月完成数千万元A轮融资。五年后“合”不过锦篮基因的每一步进展与成就，似乎都与五加和基因脱离不了关系。双方一路相辅相成，展开了深入合作。细看锦篮基因研发管线进展，目前旗下管线都还处于相对早期阶段，开发了脊髓性肌萎缩症(SMA) 基因治疗药物、高甘油三血症基因治疗药物、庞贝病基因治疗药物、家族性 LCAT缺乏症基因治疗药物在内的多条基因治疗药物研发管线。至今，锦篮基因已获6项IND，进展较快的分别为GC101、GC304、GC301，已进入临床试验阶段，其中 GC101 注射液系国内唯一采用鞘内给药策略的基因治疗药品，GC301 注射液系国际首个 AAV 递送治疗婴儿型庞贝病的基因治疗药物。拿 GC101 注射液来说，据锦篮基因透露，该产品便由北京瑞希罕见病基因治疗技术研究所进行前期探索性研究,五加和基因及其子公司北京京谱迪科技有限公司完成制品生产及药学研究，锦篮基因完成药理研究、临床方案拟定及药品注册申报，并将开展后续临床研究及临床试验。如董小岩曾言“锦蓝基因5个跟 AAV 相关的罕见病基因治疗药物的IND申请全是五加和基因帮助做的。”吴小兵也曾表示，锦篮基因GMP产品制备及CMC文件资料形成均来自于五加和基因的CDMO商业服务支持。在各自辉煌发展五年后，一路相辅相成的两家公司决定战略重组。此外，董小岩曾透露，五加和基因2022年启动了在北交所上市的计划。随着此次战略合并重组，五加和基因北交所上市的规划则不了了之。而今，在完成与锦篮基因重组合并后，五加和基因便成为锦篮公司基因药物生产中心，其原有 CDMO 业务将由其子公司北京京谱迪基因科技有限公司承接开展。公开资料显示，北京京谱迪基因科技有限公司于 2018 年成立，法定代表人董小岩，不过此前在产业界鲜有消息。登记邮箱信息订阅E药经理人信息服务扫描二维码精彩推荐CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化｜猎药人系列专题启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 | 荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药｜再鼎医药跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

基因疗法临床申请