Hyponatremia is a common electrolyte imbalance which often results from hormonal disregulation. The study aims to investigate whether the apelin hormone, which plays a role in regulating salt and water balance in the body, can be used to treat hyponatremia.
The study will involve healthy volunteers who will be given a medication that causes their bodies to retain water, thus inducing a temporary hyponatremia state. The researchers will measure the volunteers' blood and urine electrolyte levels to see how these are influenced by apelin administration. As comparison, the same measurements will be done in volunteers dosed with placebo instead of apelin.
The researchers believe that apelin may be able to help to correct hyponatremia by increasing urine output. If the study focused in the healthy volunteers population is successful, the investigators will assess the effect of apelin administration in patients with chronic hyponatremia.
The study's hypothesis is that intravenous apelin will increase urinary excretion and sodium levels in healthy participants with artificially induced hyponatremia.

开始日期2024-03-01

申办/合作机构

Universitätsspital Basel

NCT03449251 / Active, not recruiting临床2期

A Series of Pilot Studies to Evaluate the Haemodynamic and Metabolic Effects of Apelin and Relaxin in Healthy Humans, Subjects With Increased Weight and Patients With Type 2 Diabetes Mellitus

Type two diabetes mellitus (T2DM) is a common, long term metabolic disorder characterised by hyperglycaemia (high blood glucose) resulting from insulin resistance and relative insulin insufficiency. The risk of developing insulin resistance and subsequently T2DM is increased by being overweight and also through a sedentary lifestyle. As the onset can be gradual, physiological damage may have occurred prior to diagnosis. Diabetes is associated with the development of microvascular complications (diabetic nephropathy, neuropathy, and retinopathy), and macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke). While there are many treatments available for T2DM, these complications may still arise, leading to significant morbidity and mortality. There is therefore an urgent need to identify novel signalling pathways that may contribute to the development of diabetes related complications. The identification of these pathways may ultimately lead to the development of new therapies targeting better blood glucose control and preventing these subsequent complications.
Both animal and human studies have indicated that two endogenous peptides, apelin and relaxin both act as vasodilators in the human cardiovascular system and could also have beneficial action in T2DM. Therefore, we aim to carry out experimental medicine studies to test this hypothesis, and explore the signalling pathway in the human vascular system.

开始日期2018-03-28

申办/合作机构

Cambridge University Hospitals NHS Foundation Trust

[+3]

NCT02724566 / Completed临床1期IIT

Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

Preclinical studies have demonstrated in mouse models that (PYR1)-apelin-13 exerts a glucose-regulating action in vivo. The (PYR1)-apelin-13 effect on insulin sensitivity in healthy overweighed volunteers has been previously assessed in a phase I clinical trial (APELINS study; NCT02033473). The APELINS-2 clinical trial aims to expand the initial proof of concept to the population targeted by future innovative insulin-sensitizing therapies: patients living with type 2 diabetes.

开始日期2016-05-01

申办/合作机构

Société Francophone Du Diabete

100 项与爱帕琳肽相关的临床结果

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100 项与爱帕琳肽相关的转化医学

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100 项与爱帕琳肽相关的专利（医药）

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926

项与爱帕琳肽相关的文献（医药）

2024-04-01·The Journal of steroid biochemistry and molecular biology

Possible role of apelin on the ovarian steroidogenesis and uterine apoptosis of infantile mice: An in vitro study

Article

作者: Roy, Vikas Kumar ; Gurusubramanian, Guruswami ; Anima, Borgohain

The expression of adipokines is well-known in the ovary and uterus. Recently we have shown that apelin and its receptor, APJ are developmentally regulated in the ovary and uterus of mice with elevation at postnatal day 14 (PND14). However, its role in the ovary and uterus of PND14 has not been investigated. Thus, we aimed to unravel the role of the apelin system (by APJ antagonist, ML221) on ovarian steroid secretion, proliferation, and apoptosis along with its role in uterine apoptosis in PND14 mice by in vitro approaches. The treatment of ML221 decreased estrogen, testosterone, and androstenedione secretion while increasing the progesterone secretion from the infantile ovary. These results suggest that apelin signaling would be important for ovarian estrogen synthesis in infantile mice (PND14). The abundance of 3β-HSD, 17β-HSD, aromatase, and active caspase3 increased in the infantile ovary after ML221 treatment. The expression of ERs and BCL2 were also down-regulated by ML221 treatment. The decreased BCL2 and increased active caspase3 by ML221 suggest the suppressive role of apelin on ovarian apoptosis. The APJ antagonist treatment also down-regulated the ER expression in the uterus along with increased active caspase3 and decreased BCL2 expression. In conclusion, apelin signaling inhibits the ovarian and uterine apoptosis via estrogen signaling in the ovary and uterus.

2024-03-01·Biochimica et biophysica acta. Biomembranes

Localized apelin-17 analogue-bicelle interactions as a facilitator of membrane-catalyzed receptor recognition and binding

Article

作者: Rainey, Jan K ; Murza, Alexandre ; Frampton, John P ; Phạm, Trần Thanh Tâm ; Marsault, Éric

The apelinergic system encompasses two peptide ligand families, apelin and apela, along with the apelin receptor (AR or APJ), a class A G-protein-coupled receptor. This system has diverse physiological effects, including modulating heart contraction, vasodilation/constriction, glucose regulation, and vascular development, with involvement in a variety of pathological conditions. Apelin peptides have been previously shown to interact with and become structured upon binding to anionic micelles, consistent with a membrane-catalyzed mechanism of ligand-receptor binding. To overcome the challenges of observing nuclear magnetic resonance (NMR) spectroscopy signals of a dilute peptide in biological environments, ¹⁹F NMR spectroscopy, including diffusion ordered spectroscopy (DOSY) and saturation transfer difference (STD) experiments, was used herein to explore the membrane-interactive behaviour of apelin. NMR-optimized apelin-17 analogues with 4-trifluoromethyl-phenylalanine at various positions were designed and tested for bioactivity through ERK activation in stably-AR transfected HEK 293 T cells. Far-UV circular dichroism (CD) spectropolarimetry and ¹⁹F NMR spectroscopy were used to compare the membrane interactions of these analogues with unlabelled apelin-17 in both zwitterionic/neutral and net-negative bicelle conditions. Each analogue binds to bicelles with relatively weak affinity (i.e., in fast exchange on the NMR timescale), with preferential interactions observed at the cationic residue-rich N-terminal and mid-length regions of the peptide leaving the C-terminal end unencumbered for receptor recognition, enabling a membrane-anchored fly-casting mechanism of peptide search for the receptor. In all, this study provides further insight into the membrane-interactive behaviour of an important bioactive peptide, demonstrating interactions and biophysical behaviour that cannot be neglected in therapeutic design.

2023-12-31·Renal failure

Apelin-13 alleviates contrast-induced acute kidney injury by inhibiting endoplasmic reticulum stress

Article

作者: Wu, Ting ; Kang, Yi-Xin ; Duan, Shao-Bin ; Wu, Xi ; Yan and, Ping ; Luo, Xiao-Qin ; Deng, Ying-Hao ; Wang, Lin ; Liu, Qian ; Wang, Hong-Shen

Contrast-induced acute kidney injury (CI-AKI) is a severe complication associated with significant morbidity and mortality, and effective therapeutic strategies are still lacking. Apelin is an endogenous physiological regulator with antioxidative, anti-inflammatory and antiapoptotic properties. However, the role of apelin-13 in CI-AKI remains unclear. In our study, we found that the protein expression levels of apelin were significantly downregulated in rat kidney tissues and HK-2 cells during contrast media treatment. Moreover, we explored the protective effect of apelin-13 on renal tubule damage using in vitro and in vivo models of CI-AKI. Exogenous apelin-13 ameliorated endoplasmic reticulum stress, reactive oxygen species and apoptosis protein expression in contrast media-treated cells and rat kidney tissues. Mechanistically, the downregulation of endoplasmic reticulum stress contributed critically to the antiapoptotic effect of apelin-13. Collectively, our findings reveal the inherent mechanisms by which apelin-13 regulates CI-AKI and provide a prospective target for the prevention of CI-AKI.

项与爱帕琳肽相关的新闻（医药）

2024-06-21

·BioSpace

BioAge Labs Presents Preclinical Data for Apelin Receptor Agonist Azelaprag for Obesity Demonstrating Significant Improvements in Weight Loss and Body Composition When Combined with Incretin Drugs

Oral presentation delivered by Chief Medical Officer Paul Rubin, MD, at the American Diabetes Association's 84th Scientific Sessions, the world’s largest diabetes conference RICHMOND, Calif.--(BUSINESS WIRE)-- BioAge Labs, Inc. ("BioAge"), a clinical-stage biotechnology company developing therapeutic candidates for metabolic diseases, such as obesity, by targeting the biology of aging, today announced preclinical data for its lead product candidate azelaprag, an orally available small molecule agonist of the apelin receptor APJ, in combination with incretin agonists for the treatment of obesity. The data were presented in a talk by BioAge’s Chief Medical Officer and EVP-Research Paul Rubin, MD, at the American Diabetes Association's 84th Scientific Sessions. The conference, being held June 21–24 in Orlando, convenes more than 12,000 leading physicians, scientists, and health care professionals and features the latest scientific and therapeutic findings in diabetes. In a mouse model of obesity, the addition of azelaprag to the GLP-1/GIP receptor agonist tirzepatide increased total weight loss to 39%, approximately double that of tirzepatide monotherapy, restoring body weight to the range observed in lean control mice. Furthermore, the combination restored body composition and muscle function to that of lean controls. Similar results were observed when azelaprag was combined with semaglutide, a GLP-1 receptor agonist. Importantly, the synergistic weight loss observed in animals on combination therapy was not due to a further decrease in food intake. "We are highly encouraged by these preclinical data, which highlight the potential of azelaprag to significantly improve the weight loss and metabolic benefits of incretin therapy, the current standard of care for obesity," said Kristen Fortney, Ph.D., CEO of BioAge. "Given its oral availability and favorable tolerability profile, we believe azelaprag is ideally suited for combination use with incretin drugs and could enable a new generation of patient-friendly, all-oral obesity regimens that could rival or even surpass the efficacy of injectables while also promoting healthy body composition." Azelaprag is a potential first-in-class oral agonist of the apelin receptor APJ. Apelin is an exercise-induced signaling molecule (exerkine) that acts on APJ to mediate many of the metabolic benefits of physical activity. In a Phase 1b trial, azelaprag promoted muscle metabolism and prevented muscle atrophy in healthy older volunteers on bed rest (link). The study also showed that azelaprag shifted circulating protein biomarkers in a manner consistent with its function as an exercise mimetic, increasing predicted resting energy expenditure and cardiorespiratory fitness. BioAge plans to initiate a Phase 2 trial in mid-2024 evaluating azelaprag in combination with tirzepatide (Zepbound®) in older adults with obesity (link). The study is being conducted in collaboration with Eli Lilly and Company, which is providing tirzepatide, and Lilly's Chorus clinical development organization, which is advising on trial design and execution. Presentation Details: Title: Apelin Receptor Agonist Azelaprag Increases Weight Loss in Diet-Induced Obese Mice on Incretin Agonists and Restores Body Composition and Muscle Function to that of Lean Controls Abstract number: 118-OR Session: Beyond Glucose and Weight Reduction—Additional Effects of Incretin-Based Therapies Date/time: Friday, June 21, 2024, 4:15 – 4:30 PM Presenter: Paul Rubin, MD, Chief Medical Officer and EVP-Research, BioAge Labs About BioAge Labs, Inc. BioAge is a clinical-stage biotechnology company developing therapeutic product candidates for metabolic diseases, such as obesity, by targeting the biology of human aging. The company’s lead product candidate, azelaprag, is an orally available small molecule agonist of APJ that promoted metabolism and prevented muscle atrophy on bed rest in a Phase 1b trial. In mid-2024, BioAge plans to initiate a Phase 2 trial of azelaprag in combination with tirzepatide for the treatment of obesity in older adults. Azelaprag has potential as an oral regimen to amplify weight loss and improve body composition in patients on obesity therapy with incretin drugs. BioAge is also developing BGE-100, a structurally novel NLRP3 inhibitor. BioAge’s preclinical programs, based on novel insights from the company’s discovery platform built on human longevity data, also address key pathways in metabolic aging.

临床1期临床2期

2024-05-15

·BioSpace

BioAge Labs Announces Inaugural Scientific Advisory Board to Support Advancement of Novel Therapeutics Targeting Metabolic Aging

Newly appointed advisors are world-renowned experts in obesity, diabetes, and cardiometabolic diseases, spanning basic biology to late-stage development RICHMOND, Calif.--(BUSINESS WIRE)-- BioAge Labs, Inc. ("BioAge"), a clinical-stage biotechnology company developing therapeutic candidates for metabolic diseases, such as obesity, by targeting the biology of aging, today announced the formation of its Scientific Advisory Board (SAB). The SAB is composed of world-renowned leaders with expertise spanning metabolic disease biology, obesity medicine, and clinical development of blockbuster therapeutics. The SAB will work closely with BioAge's leadership team to advance the company's pipeline of novel treatments for age-related chronic metabolic diseases into mid- and late-stage clinical development. "We are thrilled to be working with this esteemed group of expert scientists and drug developers as we pioneer new approaches to treating age-related metabolic diseases," said Kristen Fortney, Ph.D., co-founder and Chief Executive Officer of BioAge. "Our advisors' wealth of experience across all phases of drug development, from scientific discovery through approval and commercialization, will be instrumental as we advance our lead product candidate into Phase 2 clinical trials for obesity." BioAge's lead product candidate azelaprag is an orally administered agonist of the apelin receptor APJ that has the potential to mimic the effects of exercise. In preclinical studies, azelaprag has demonstrated the ability to significantly increase weight loss while improving body composition and metabolic parameters when administered in combination with GLP-1 receptor agonists. The company plans to initiate a Phase 2 trial in mid-2024 evaluating azelaprag in combination with tirzepatide (Zepbound®) for the treatment of obesity in older adults (link). The members of the BioAge SAB are: Caroline M. Apovian, MD, FACP, FTOS, DABOM, Professor of Medicine at Harvard Medical School and Co-Director of the Center for Weight Management and Wellness (CWMW) at Brigham and Women’s Hospital. A leading expert in clinical management of obesity, Dr. Apovian has co-authored multiple U.S. and international obesity treatment guidelines. She co-founded the American Board of Obesity Medicine and served as President of the Obesity Society from 2017–2018. Cedric Dray, Ph.D., Associate Professor at INSERM and faculty member at the RESTORE Geroscience Center at Université de Toulouse III-Paul Sabatier. Prof. Dray has published multiple papers describing his pioneering work on apelin and is a world expert on the biology of the apelin pathway in aging, muscle physiology, and metabolic disease. The apelin pathway is the target of BioAge’s lead product candidate, azelaprag, expected to enter a Phase 2 trial for obesity starting in mid-2024. William Evans, Ph.D., Adjunct Professor of Human Nutrition at UC Berkeley and Adjunct Professor of Medicine (Geriatrics) at Duke University. As a former VP at GSK, he led the company's Muscle Metabolism Discovery Performance Unit, and has served as an investigator in multiple clinical trials of muscle aging. Dr. Evans was the first to describe sarcopenia, the age-related loss of muscle mass and strength. His research on muscle metabolism, aging, and functional capacity has resulted in more than 350 publications with more than 80,000 citations. Alexander Fleming, M.D., Founder and Executive Chairman of Kinexum, which provides strategic and operational guidance throughout the process of clinical development and drug commercialization. As a supervisory physician at the US FDA from 1986-98, Dr. Fleming led landmark regulatory reviews for first-in-class drugs for diabetes and other metabolic diseases including metformin, statins and insulin analogs. He also heads the not-for-profit Kitalys Institute, founded to catalyze progress in developing drugs and other ways to increase healthy longevity. Narimon Honarpour, M.D., Ph.D., Senior VP and Head of Global Development at Amgen, where he leads a team responsible for shaping program clinical development strategies through deep disease state knowledge and generating clinical trial evidence to enable pipeline progression. Since joining Amgen in 2011, Dr. Honarpour has held diverse roles across both cardiovascular and inflammation therapeutic areas. In 2019, he became head of Translational Medicine, and in his most recent prior role served as VP-Global Development for the General Medicine Therapeutic Area Head and JAPAC Development Head. Tim Rolph, D.Phil., Chief Scientific Officer and Co-Founder of Akero Therapeutics, a company devoted to developing novel therapies for patients with serious metabolic diseases, including efruxifermin, an FGF21 analog, for metabolic dysfunction–associated steatohepatitis (MASH). Previously, as Chief Scientific Officer of Pfizer's Cardiovascular & Metabolic Disease unit, Dr. Rolph oversaw the development of Steglatro (ertugliflozin) for type 2 diabetes and discovery of oral small-molecule GLP1R agonists and inhibitors of PCSK9 and DGAT2. "We are looking forward to working closely with the renowned experts on our SAB to harness the biology of apelin, an exercise mimetic, to improve the lives of patients living with obesity and other metabolic conditions,” said Eric Morgen, MD, co-founder and Chief Operating Officer of BioAge. “We will also leverage their broad expertise in drug development for metabolic diseases to guide the continued advancement of the other programs in our metabolic disease pipeline.” About BioAge Labs, Inc. BioAge is a clinical-stage biotechnology company developing therapeutic product candidates for metabolic diseases, such as obesity, by targeting the biology of human aging. The company’s lead product candidate, azelaprag, is an orally available small molecule agonist of APJ that promoted metabolism and prevented muscle atrophy on bed rest in a Phase 1b trial. In mid-2024, BioAge plans to initiate a Phase 2 trial of azelaprag in combination with tirzepatide for the treatment of obesity in older adults. Azelaprag has the potential as an oral regimen to amplify weight loss and improve body composition in patients on obesity therapy with incretin drugs. BioAge is also developing BGE-100, a structurally novel NLRP3 inhibitor, with plans to IND by the end of 2024. BioAge’s preclinical programs, based on novel insights from the company’s discovery platform built on human longevity data, also address key pathways in metabolic aging.

临床2期高管变更临床1期

2024-04-02

·同写意

通往减肥药下半场的“黄金门票”

大会由扬州市人民政府主办，同写意专业策划，以“打造生物医药新质生产力”为主题，邀请众多行业领袖和先锋人物一起取势明道，就如何打造中国医药新质生产力，面向未来创新药如何立项，资本寒冬下的创新药BD与出海，GLP-1&小核酸药物以及抗体药的质量与生产四大主题展开深度研讨，为行业发展提供方向性指引。GLP-1引发的药王争霸赛，创造了前所未有的盛况。有目共睹，第一波“泼天富贵”已被诺和诺德、礼来瓜分殆尽，这两家公司市值纷纷暴涨。礼来市值突破7200亿美元，诺和诺德则在最近FDA批准司美格鲁肽新适应症之后，市值一度接近6000亿。财报显示，2023年诺和诺德司美格鲁肽销售额约211.58亿美元，礼来的度拉糖肽则创造71.3亿美元收入，替尔泊肽获批首年销售额也达到51.63亿美元。从增速来看，替尔泊肽远超司美格鲁肽最初的表现。减重市场的潜力依然在火热挖掘中。“大哥”“二哥”纷纷买厂建厂催产能，明面上，市场占领是当下这两家公司兵刃相接的主要触点。但长期结果还要回归医药市场的本质来看，患者需求是药物“适者生存”的根本法则。目前减重药物存在巨大缺陷——减重往往伴随肌肉减少，且对“骨骼肌和心肺肌都有明显的影响”。有研究显示，司美格鲁肽受试者减掉的体重中近40%为肌肉，而肌肉减少会增加患心血管疾病、骨质疏松症的风险，替尔泊肽也难以避免这一问题，这无疑创造了新的需求。蝴蝶扇动翅膀，增肌剂在无意间被“带飞”，很可能成为减肥药市场的下一个赛点。越来越多的公司开始推进增肌药物试验，有分析师预测，其市场将达到1000亿美元。这些药物最初设计用于构建、保存或再生骨骼肌，以治疗退行性疾病或老化引起的肌肉萎缩。而现在，它们最受关注的用途是，用于和治疗肥胖症的GLP-1激动剂联合进行测试，以抵御减重的副作用。投资者也开始将目光转向减脂增肌。BioAge Labs是该领域中一家代表公司，今年2月13日宣布已完成由Sofinnova Investments领投的1.7亿美元的D轮融资，礼来也选择这家Biotech作为合作伙伴。当然，长远来看，增肌并不总是配角位，在人类抗衰大健康领域还有更广阔的市场，有望带来更多临床和投资机会。1礼来押注ActRII和Apelin相比规规矩矩增产、想要坐稳“减肥一哥”宝座的诺和诺德来说，后来挑战者礼来的翻盘策略更耐人寻味。去年7月，礼来以19.25亿美元高价收购Versanis，获得其ActRIIA/B 单抗Bimagrumab。10月，礼来宣布与BioAge达成合作，将替尔泊肽和BioAge的其口服Apelin受体激动剂Azelaprag联用，进行II期临床试验。本质上这是一件事。礼来正在探索减少脂肪同时防止肌肉流失的产品组合，这家巨头最关注肌肉生长抑制素和艾帕素领域（ActRII受体和Apelin受体靶点）。1997年，科学家发现肌肉生长抑制素 (GDF8) 是骨骼肌大小的关键调节因子。早期研究显示，缺乏肌肉生长抑制素的老鼠和狗，其肌肉质量是野生型的两倍。随后大量研究证实，肌生长抑制素是肌肉质量的主要负调节因子，主要通过激活素II型受体 (ActRII) 发挥作用。包括Activin和GDF11在内的一些ActRII配体，被认为是肌肉质量的负调节剂。它们与肌生长抑制素一起与细胞膜上的ActRIIA或ActRIIB受体结合，ActRIIB最初被认为是肌生长抑制素的主要受体。ActRII在肌肉组织中的生物学机制（图源：Versanis公司官网）Versanis开发的Bimagrumab单抗是该靶点领域的代表者，此前已收获大量积极数据。其在一项针对2型糖尿病的超重或肥胖患者的II临床试验中48周数据显示，相比安慰剂，Bimagrumab治疗组的体重下降了6.5%，造成患者约22%脂肪质量的损失，并增加4.5%的无脂体重。同时，Bimagrumab治疗组在停药12周内并未观察到体重的增加。关于联用效果，一项Bimagrumab和司美格鲁肽联用的动物试验显示，用药2周后，该产品组合导致肥胖小鼠大于30%的脂肪损失，并增加了5%的瘦肉质量。目前，Bimagrumab正在进行临床IIb期BELIEVE研究，评估单药或联合司美格鲁肽48周治疗后在超重或肥胖的成年人中的效果。另一边，牵手礼来的BioAge在今年2月宣布完成1.7亿美元的D轮融资，主要用于推进Azelaprag与替尔泊肽联合治疗肥胖的2期临床试验，预计将于今年年中正式开启。Azelapra是Apelin受体的APJ激动剂，模拟了exerkine Apelin的活性，这是一种在运动后释放的“运动因子”多肽，作用于骨骼肌、心脏和中枢神经系统，调节代谢并促进肌肉再生。BioAge的研究显示，人的一生中，Apelin总体水平会逐渐下降，而Apelin水平较高的人具有更强的身体功能和更长的寿命。在2022年12月对227名65岁或以上老年人进行的一项Ib临床试验中，该药物可以显著预防老年人的肌肉萎缩。BioAge联合创始人、首席执行官Kristen Fortney曾公开表示，Azelaprag和Mounjaro联用的产品组合在I期研究和动物模型中均保留了瘦肉体组织，与单独使用Mounjaro相比，体重减轻了10-15%，有效地“增压”了减肥。不仅能看到减肥效果的放大，还看到了身体成分和功能的改善。巨头的收购与合作，往往预示着下一个热门竞逐标的。礼来的一系列布局似乎正指向，增肌是减肥市场的下一个赛点。2凭借增肌药物中场入局虽然没能赶上第一波东风，但还有机会在减肥市场分一杯羹，再生元、罗氏、辉瑞、阿斯利康等药企纷纷朝增肌药物联用展开动作。近日，再生元重申了2024年进入减肥赛道的计划——公司将开始测试其防止肌肉流失药物与司美格鲁肽的组合，预计在今年年中开始一项II期研究，测试一系列不同剂量和组合的司美格鲁肽、trevogrumab（一种抗肌肉生长抑制素抗体）和garetosmab（一种抗激活素a抗体）。Garetosmab（REGN 2477）是一种全人IgG4单克隆抗体，可特异性抑制激活素A (activin A)。Garetosmab可用于进行性骨化性纤维发育不良。再生元称，预计将于5月开展Garetosmab和司美格鲁肽的联用试验，探索提高减肥质量且停药不反弹的解决方案。此外，这家公司还在推进基于遗传学的肥胖研究，重点关注GPR75靶点，而资料显示GPR75基因与肥胖显著相关。再生元正在通过内部和外部的组合开发，拓展siRNA/小核酸、小分子和抗体等多种GPR75靶点的疗法。罗氏也有凭借增肌药物联用入局减肥市场的想法，自去年的收购案之后，在一些公开发言中均有透露。去年年底，罗氏以超30亿美金收购了Carmot Therapeutics，一次获得了3款GLP类药物。该公司希望将抗肌肉生长抑制素抗体RO7204239与肠促胰岛素治疗相结合。RO7204239最初被测试用于增强脊髓性肌萎缩症患者的肌肉，但罗氏首席执行官Thomas Schinecker表示，该药物在弥补GLP-1缺陷方面能够发挥重要作用。辉瑞于2022年以116亿美元收购的Biohaven，同样也在推进增肌药物和司美格鲁肽的联合使用。目前，Biohaven正在进行taldefgrobep alfa（一种肌肉生长抑制素抑制剂）的临床III期试验，以改善脊髓性肌萎缩症的肌肉质量。肥胖小鼠模型中，该药物被证明成功地在减肥期间保持肌肉质量，促使Biohaven在II期试验中将其与司美格鲁肽联合使用。阿斯利康同样正在积极探索增肌降脂联合疗法。该公司去年以1.85亿美元收购了诚益生物口服GLP-1药物的非中国权利，并打算将其与AZD6234结合试验。还有一些靶点机制同样展现出增肌潜力。例如，mTORC1（雷帕霉素复合体1的机制靶点），参与肌肉再生。mTORC1激活可促进肌肉生长，但如果持续受到刺激，它也会通过激活蛋白酶体降解来诱导肌肉分解。长期的雷帕霉素治疗对老化的骨骼肌具有积极的作用，可以保持肌肉的大小、功能和神经肌肉连接（NMJ）完整性。此外，有研究人员希望通过刺激肌肉干细胞、调整细胞外基质的硬度等变量或改造细胞外囊泡来提供治疗，从而促进肌肉再生。Immunis和Juvena Therapeutics针对这一机制进行研究，专注于肌肉干细胞分泌成分，包括生长因子、细胞因子、趋化因子和细胞外基质成分。分泌蛋白会促进运动后的增殖，或增强细胞相互作用以加速伤口愈合，但它会随着年龄的增长而显著下降。Biophytis则重点关注与年龄相关的肌肉减少症和杜氏肌营养不良等神经肌肉疾病之间的共同途径。其主要候选药物是ruvembri（BIO101），是一款针对MAS受体的小分子药物。MAS受体存在于心肺和骨骼肌中。MAS激活下游AKT和AMPK激酶通路，分别刺激蛋白质合成和能量产生。相比海外的热火初起，国内还未形成增肌药物潮流。港股上市公司来凯医药可以说是最先作出反应的一家，本月上旬，该公司宣布其减脂增肌药物LAE102已完成中美双报。值得注意的是，目前全球在研ActRII药物中，Bimagrumab和LAE102是目前唯二开发肥胖适应症的候选药物。翰森制药也有意在ActRII受体靶点方向展开布局，2021年12月翰森药业曾以2000万美元加高达1.705亿美元里程碑从Keros引入KER-050，该药物家族蛋白是血红细胞和血小板生成以及肌肉和骨骼生长、修复和维护的主要调节因子，具备增肌药物潜力。3不可限量的消费和抗衰市场除了作为减肥“伴侣”外，增肌药物真正的蓝海市场在塑形消费和人类抗衰领域。从消费市场来看，增肌与减脂需求并驾齐驱，且随着审美观念的转变，增肌或将囊括更多潜在消费群体。同时，从广泛的人类抗衰领域来看，抗衰老将是一个必选项。研究显示，从30岁开始，人类每十年平均会失去3-8%的肌肉质量，60岁以后这种情况会加速。在老年群体中，肌肉流失或肌肉减少症会导致活动能力下降，并与跌倒、虚弱和心血管疾病有关。梅奥诊所Robert和Arlene Kogod表示，针对肌肉减少症最关键的问题在于，它通常被视为衰老和长期不动的症状，而不是一种独立的疾病。现阶段，肌肉减少症的标准干预措施包括力量训练和营养咨询，以确保患者摄入足够的蛋白质。从理论上讲，这种方法是有效的。但是，在有其他慢性病、炎症、受伤或行动不便的患者身上，并不总是奏效，因此需要有效药物的干预。随着全球人口老龄化加剧和抗衰老理念的普及，越来越多的消费者开始关注抗衰老措施。调查显示，59.2%的人在20-30岁就对衰老产生焦虑，95.3%的人在50岁之前对衰老产生焦虑。因此，有分析师表示，抗衰老市场潜力甚至更高于减肥。而增肌药物横跨减肥抗衰两大市场，显然前景可期。参考文献：1.Arnold, C. After obesity drugs’ success, companies rush to preserve skeletal muscle. Nat Biotechnol 42, 351–353 (2024).2.各公司官网更多优质内容，欢迎关注↓↓↓

并购财报临床2期上市批准核酸药物

100 项与爱帕琳肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	爱帕琳肽	-	-

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
心血管疾病	临床2期	英国	AstraZeneca PLC	2018-03-28
2型糖尿病	临床2期	英国	AstraZeneca PLC	2018-03-28

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ERA2023	N/A	慢性肾病	30	Apelin (Patients with CKD)	顧鹹遞醖齋選壓獵膚觸(膚鏇構淵選齋壓衊構膚) = 製餘繭願艱壓構網醖憲鹽顧願積夢鹽糧積簾窪 (製鑰衊鑰觸簾簾鏇蓋鬱 ) 更多	-	2023-06-15
				Apelin (Healthy volunteers)	顧鹹遞醖齋選壓獵膚觸(膚鏇構淵選齋壓衊構膚) = 鏇壓網窪蓋艱壓壓顧範鹽顧願積夢鹽糧積簾窪 (製鑰衊鑰觸簾簾鏇蓋鬱 ) 更多
ERA2023	N/A	慢性肾病	24	apelin (Healthy volunteers)	選範構繭構繭齋獵糧繭(繭觸糧醖夢窪夢淵憲遞) = 鬱醖糧糧壓鹽艱鬱夢選蓋窪壓衊範觸選艱夢齋 (襯壓選廠網鑰獵蓋獵蓋 ) 更多	-	2023-06-15
				apelin (Chronic kidney disease)	選範構繭構繭齋獵糧繭(繭觸糧醖夢窪夢淵憲遞) = 鹹願積蓋襯廠顧鬱構構蓋窪壓衊範觸選艱夢齋 (襯壓選廠網鑰獵蓋獵蓋 ) 更多
EASD2015	N/A	-	-	Apelin	夢簾積繭夢餘壓繭構鹹(鏇襯鹽顧糧醖壓觸廠餘) = Average frequency of NO hypothalamic release is significantly reduced following infusion of low-doses of apelin in the digestive tract (0,11 ± 0,003 Hz vs 0,12 ± 0,002 for control; P<0.001) 網獵觸淵鏇願衊觸遞鹹 (鹽積糧糧願鏇鑰蓋齋襯 ) 更多	-	2015-09-16
				apelin
ERS2015	N/A	apelin	11	Pyr1apelin-13	夢憲構窪鬱簾淵獵觸選(鹽艱鏇鏇壓醖鹹繭顧壓) = 願齋廠鬱製衊鹹網積構範範製鹽簾糧廠膚襯顧 (網顧窪膚蓋鬱鹹鑰蓋窪 ) 更多	不佳	2015-09-01
				Placebo	夢憲構窪鬱簾淵獵觸選(鹽艱鏇鏇壓醖鹹繭顧壓) = 廠簾膚鹽膚繭鑰網淵鏇範範製鹽簾糧廠膚襯顧 (網顧窪膚蓋鬱鹹鑰蓋窪 ) 更多
Pubmed \| J Mol Biol	N/A	-	-	Apelin-13	艱糧糧憲壓遞鬱蓋醖獵(淵製觸獵齋鏇鬱選醖鹹) = Apelin also increased I(Na) "window" current by up to 600% 艱範鬱餘膚衊窪淵鏇醖 (顧餘窪醖鏇襯顧窪鹽廠 )	-	2010-04-01
				Apelin-17