更新于：2024-05-01

NPY2R

神经肽Y受体2型

更新于：2024-05-01

基本信息

别名

Neuropeptide Y receptor type 2、neuropeptide Y receptor Y2、NPY-Y2 receptor

+ [3]

简介

Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PYY > NPY > PYY (3-36) > NPY (2-36) > [Ile-31, Gln-34] PP > [Leu-31, Pro-34] NPY > PP, [Pro-34] PYY and NPY free acid.

关联

项与 NPY2R 相关的药物

NNC-0165-1875

靶点-

作用机制

NPY2R激动剂

在研机构

Novo Nordisk A/S

原研机构

Novo Nordisk A/S

在研适应症

肥胖

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

CIN-110

靶点-

作用机制

NPY2R激动剂

在研机构

CinFina Pharma

原研机构

CinFina Pharma

在研适应症

肥胖

非在研适应症-

最高研发阶段临床申请批准

首次获批国家/地区-

首次获批日期1800-01-20

PYY-1119

靶点-

作用机制

NPY2R激动剂

在研机构

Takeda Pharmaceuticals LLC

原研机构

Takeda Pharmaceuticals LLC

在研适应症

肥胖

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 NPY2R 相关的临床试验

NCT05110664 / Not yet recruitingN/AIIT

A Double-blind, Cross-over, Placebo-controlled, Proof-of-concept Study Using Oral Peptide YY3-36 Solution to Investigate the Mechanistic Role of Lingual PYY in Regulating Appetite, Energy Intake and Food Preference in People With Overweight/Obesity

A double-blind, cross-over, placebo-controlled, proof-of-concept study using oral peptide YY3-36 solution to investigate the mechanistic role of lingual PYY in regulating appetite, energy intake and food preference in people with overweight/obesity. The aim of this study is to investigate the mechanistic role of lingual PYY in regulating appetite, energy intake and food preference in people with overweight/obesity.

开始日期2022-02-01

申办/合作机构

University College London

[+1]

NCT04969939 / Completed临床2期

Investigation of Efficacy and Safety of NNC0165-1875 as add-on to Semaglutide for Weight Management in Subjects With Obesity

The study is looking at a new medicine to help people lose weight. In this study participants will either get semaglutide and NNC0165-1875 or semaglutide and a "dummy" medicine (placebo). Which treatment participants get is decided by chance. Participants will get 2 injections per week, on the same day. Participants will have to take the study medicine by use of a pre-filled pen. A pen is a medical tool with a needle used for injections under the skin. The study doctor or staff will show participants how. The study will last for about 26 weeks. Participants will have 17 visits at the clinic with the study doctor. At 4 of the clinic visits participants cannot eat and drink (water is allowed until 2 hours prior to the visit) for 8 hours before the visit.Women: Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period. Women who are able to become pregnant can participate if they agree to use contraception during the study.

开始日期2021-07-15

申办/合作机构

Novo Nordisk A/S

NCT03707990 / Completed临床1期

A First Human Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of Single Doses of NNC0165-1875 as Monotherapy and in Combination With Semaglutide in Subjects With Overweight or Obesity

The study is looking at possible new medicines for weight control in people with high body weight. The study looks at how the new medicines work in the body. The study consists of two parts. If participants take part in Part 1, they will either get a single dose of NNC0165-1875 or a "dummy" medicine (placebo). If participants take part in Part 2, they will either get a single dose of NNC0165-1875 or "dummy" medicine and also a single dose of semaglutide. Which treatment participants get is decided by chance. For Part 1 participants will get 1 injection. For Part 2 participants will get 2 injections. A study nurse at the clinic will inject the medicine with a thin needle in a skin fold in the stomach. The study will last for about 9 weeks. Participants will have 7 visits to the clinic with the study doctor.

开始日期2018-10-15

申办/合作机构

Novo Nordisk A/S

100 项与 NPY2R 相关的临床结果

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100 项与 NPY2R 相关的转化医学

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0 项与 NPY2R 相关的专利（医药）

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750

项与 NPY2R 相关的文献（医药）

2024-02-08·Molecular metabolism

The Vagus Nerve Mediates the Physiological but not Pharmacological Effects of PYY_3-36 on Food Intake.

Article

作者: Aldara Martin Alonso ; Simon C Cork ; Phyllis Phuah ; Benjamin Hansen ; Mariana Norton ; Sijing Cheng ; Xiang Xu ; Kinga Suba ; Yue Ma ; Georgina Kc Dowsett ; John A Tadross ; Brian Yh Lam ; Giles Sh Yeo ; Herbert Herzog ; Stephen R Bloom ; Myrtha Arnold ; Walter Distaso ; Kevin G Murphy ; Victoria Salem

Peptide YY (PYY_3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY_3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY_3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.

2024-02-04·bioRxiv : the preprint server for biology

Dynamic regulation of CeA gene expression during acute and protracted abstinence from chronic binge drinking of male and female C57BL/6J mice.

作者: Hernán G Méndez ; Sofia Neira ; Meghan E Flanigan ; Harold L Haun ; Kristen M Boyt ; Todd E Thiele ; Thomas L Kash

Binge alcohol consumption is a major risk factor for developing Alcohol Use Disorder (AUD) and is associated with alcohol-related problems like accidental injury, acute alcohol poisoning, and black-outs. While there are numerous brain regions that have been shown to play a role in this AUD in humans and animal models, the central nucleus of the amygdala (CeA) has emerged as a critically important locus mediating binge alcohol consumption. In this study, we sought to understand how relative gene expression of key signaling molecules in the CeA changes during different periods of abstinence following bouts of binge drinking. To test this, we performed drinking in the dark (DID) on two separate cohorts of C57BL/6J mice and collected CeA brain tissue at one day (acute) and 7 days (protracted) abstinence after DID. We used qRTPCR to evaluate relative gene expression changes of 25 distinct genes of interest related to G protein-coupled receptors (GPCRs), neuropeptides, ion channel subunits, and enzymes that have been previously implicated in AUD. Our findings show that during acute abstinence CeA punches collected from female mice had upregulated relative mRNA expression of the gamma-aminobutyric acid receptor subunit alpha 2 (Gabra2), and the peptidase, angiotensinase c (Prcp). CeA punches from male mice at the same time point in abstinence had upregulated relative mRNA encoding for neuropeptide-related molecules, neuropeptide Y (Npy) and somatostatin (Sst), as well as the neuropeptide Y receptor Y2 (Npyr2) but downregulated, Glutamate ionotropic receptor NMDA type subunit 1 (Grin1). After protracted abstinence CeA punches collected from female mice had increased mRNA expression of corticotropin releasing hormone (Crh) and Npy. While CeA punches collected from male mice at the same timepoint had upregulated relative mRNA expression of Npy2r and downregulated mRNA expression of Gabra2, Grin1 and opioid receptor kappa 1 (Oprk1). Our findings support that there are differences in how the CeA of male and female respond to binge-alcohol exposure, highlighting the need to understand the implications of such differences in the context of AUD and binge drinking behavior.

2024-02-01·Endocrine connections

GLP-1 and PYY for the treatment of obesity: use of agonists and antagonists in diet-induced rats, a pilot study.

Article

作者: Marie Oertel ; Christian G Ziegler ; Michael Kohlhaas ; Alexander Nickel ; Simon Kloock ; Christoph Maack ; Vasco Sequeira ; Martin Fassnacht ; Ulrich Dischinger

OBJECTIVE:

Combination therapies with gut hormone analogues represent promising treatment strategies for obesity. This pilot study investigates the therapeutic potential of modulators of the glucagon-like peptide 1 (GLP-1) and neuropeptide Y (NPY) system using GLP-1 receptor agonists (semaglutide) and antagonists (exendin(9-39)), as well as non-selective and NPY-Y2-receptor selective peptide tyrosine tyrosine (PYY) analogues (PYY3-36/NNC0165-0020 and NNC0165-1273) and an NPY-Y2 receptor antagonist (JNJ 31020028).

METHODS:

High-fat diet (HFD)-induced obese rats were randomized into following treatment groups: group 1, non selective PYY analogue + semaglutide (n = 4); group 2, non-selective and NPY-Y2 receptor selective PYY analogue + semaglutide (n = 2); group 3, GLP-1 receptor antagonist + NPY-Y2 receptor antagonist (n = 3); group 4, semaglutide (n = 5); and group 5, control (n = 5). Animals had free access to high- and low-fat diet. Food intake, HFD preference and body weight were measured daily.

RESULTS:

A combinatory treatment with a non-selective PYY analogue and semaglutide led to a maximum body weight loss of 14.0 ± 4.9% vs. 9.9 ± 1.5% with semaglutide alone. Group 2 showed a maximum weight loss of 20.5 ± 2.4%. While HFD preference was decreased in group 2, a strong increase in HFD preference was detected in group 3.

CONCLUSIONS:

PYY analogues (especially NPY-Y2 selective receptor agonists) could represent a promising therapeutic approach for obesity in combination with GLP-1 receptor agonists. Additionally, combined GLP-1 and PYY3-36 receptor agonists might have beneficial effects on food preference.

项与 NPY2R 相关的新闻（医药）

2024-03-26

·BioSpace

CinFina Pharma Announces FDA Clearance of Investigational New Drug Application and First Participants Dosed in Phase 1 Trial of CIN-110 for the Treatment of Obesity

CIN-110 is a potent and highly selective large molecule peptide YY (PYY3-36) with an extended half-life being developed as a monotherapy and co-administration agent to induce satiety, reduce appetite and impact glucose metabolism CIN-110 is the second therapeutic in CinFina’s metabolic portfolio to reach the in-human clinical trial milestone CINCINNATI--(BUSINESS WIRE)-- CinFina Pharma, a CinRx portfolio company dedicated to advancing a portfolio of high-impact treatment options for obesity and metabolic diseases, today announced the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug Application (IND) for CIN-110, a PYY3-36 analog, allowing the first in-human clinical study to proceed. With the commencement of the trial, CinFina also announced the first cohort of participants has been dosed. The trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of CIN-110 in a randomized, double-blind, placebo-controlled, single ascending dose study in otherwise healthy subjects with obesity. “Despite the emergence of new medicines to help address the obesity epidemic, there remains an unmet medical need for therapeutics that are well tolerated for long-term treatment,” said Dr. Jon Isaacsohn, Founder and Chief Executive Officer at CinRx Pharma. “As demonstrated by promising preclinical efficacy data, CIN-110 has the potential to meet these needs and provide important therapeutic advantages to patients in monotherapy and combination settings, including durability of weight loss. We look forward to continuing to explore its safety and tolerability profiles in this important Phase 1 study.” CIN-110 is a stable and long-acting analog of PYY3-36 being developed both as a monotherapy and co-administration agent for obesity. PYY3-36 is an endogenous hormone secreted in the gut, which activates the neuropeptide Y2 receptor (Y2R) to reduce appetite and food intake. Unlike prior attempts at developing a PYY focused therapeutic, CIN-110 is uniquely designed to limit severe nausea and emesis and still deliver on the promise of effective, long-term weight loss. CIN-110 selectively binds and activates Y2R, the target for native PYY3-36. Pharmacodynamic evaluation of CIN-110 demonstrated that repeat subcutaneous dosing leads to significant reduction of food intake and body weight in obese, non-human primates and rodents. Additionally, data shows CIN-110 led to an improvement of glucose homeostasis and insulin sensitivity in animal models. The toxicology program results indicated that CIN-110 was well tolerated with no adverse findings noted in either non-human primates or rodents. The results from the preclinical efficacy and safety studies support the progression of CIN-110 to human clinical trials. “The preclinical program of CIN-110 underscores the potential for PYY to be a differentiated approach to treat obesity. This uniquely engineered molecule holds promise to expand the current therapeutic paradigm beyond GLP-1s with its selectivity, potency and half-life extension,” said Brian Murphy, M.D., Chief Medical Officer at CinRx Pharma. About CinFina Pharma: CinFina Pharma, a CinRx portfolio company, is expanding the treatment options for obesity and its associated comorbidities with a pipeline of therapeutic candidates designed to be safe, tolerable, and durable to help people lose weight and keep it off to improve their overall health. CinFina’s four therapeutic candidates are naturally occurring peptides engineered for prolonged activity which send signals in the body to control insulin secretion or feelings of satiety. Learn more at . About CinRx Pharma: CinRx Pharma is a biotech company advancing a diverse portfolio of high-impact medicines through clinical development with a unique hub-and-spoke business model. CinRx’s approach combines financing with the efficient progression of therapeutic candidates within its portfolio, each managed by CinRx’s central infrastructure and operating team. Current CinCos address areas of high unmet medical need including metabolic, gastrointestinal, and oncology. Differentiated by an asset selection process agnostic to therapeutic area, a strategic CRO partnership, and insights from thousands of development programs, CinRx identifies, funds and accelerates promising drugs with the potential to have the highest impact on patients’ quality of life. CinRx Pharma is headquartered in Cincinnati, Ohio. For more information, please visit or follow the company on X and LinkedIn.

临床申请临床结果临床1期

2023-11-07

·生物谷

Nature | 当我们晕厥时会发生什么？科学家识别出新型大脑和心脏之间的关联！

近40%的人会在其一生中至少经历一次晕厥（syncope）或晕厥发作（fainting spells），这种短暂的意识丧失，无论是疼痛、恐惧、炎热、换气过度还是其它原因所引起的，都占到了医院急诊室就诊患者的绝大一部分；然而，关于人们“晕厥”的确切根源机制在很大程度上研究人员并不清楚。近日，一篇发表在国际杂志Nature上题为“Vagal sensory neurons mediate the Bezold–Jarisch reflex and induce syncope”的研究报告中，来自加利福尼亚大学等机构的科学家们通过研究首次识别出了心脏和大脑之间与机体晕厥之间的特殊遗传通路。研究人员的独特方法之一就是将心脏视为一种感觉器官，而不是长期以来认为大脑能发送信号，而心脏只是遵循指示的观点，这项研究中，研究人员运用多种方法更好的理解了心脏和大脑之间的特殊神经连接。研究者Vineet Augustine说道，我们发现，心脏也会向大脑发送信号从而改变大脑的功能，本文研究得出的信息或许更好地理解和治疗与大脑-心脏关联有关的多种精神和神经性疾病有关。我们的研究首次全面阐明了遗传定义的心脏反射，其忠实地概括了人类晕厥、在生理学、行为学和神经网络水平上的特征。文章中，研究人员联合研究了与Bezold-Jarisch反射（BJR）相关的神经机制，BJR是一种在1867年首次被描述的心脏反射；几十年来，研究人员一直推测，以心率、血压和呼吸下降为特征的BJR或许与机体晕厥有关，但由于参与反射的神经通路目前尚不清楚，因此研究人员一直缺乏证明这一观点的信息。研究人员重点分析了称之为结神经节（nodose ganglia）的感觉簇背后的遗传学特性，其是迷走神经的一部分，能携带大脑和内脏器官（包括心脏）之间的传递信号；具体而言，迷走神经感觉神经元（VSNs，vagal sensory neurons）能将信号投射到脑干，并被认为与BJR和晕厥直接相关，在研究人员寻找新型神经通路的过程中，他们发现，能表达神经肽Y受体Y2（称之为NPY2R）的VSNs与众所周知的BJR反应密切相关。识别出新型大脑和心脏之间的关联。图片来源：Nature (2023). DOI:10.1038/s41586-023-06680-7随后研究人员在小鼠中研究了这一通路，他们惊讶地发现，当利用光遗传学（一种刺激并控制神经元的方法）主动出发NPY2R VSNs时，能自由活动的小鼠就会立刻晕倒。在这些事件中，研究人员记录了小鼠大脑中数千个神经元的数据，以及其心脏活动和面部特征的改变，包括瞳孔的直径和眨眼等。他们还采用多种方式来使用机器学习从而分析数据并确定所感兴趣的特征，研究者发现，一旦NPY2R神经元被激活，小鼠就会表现出快速的瞳孔扩张以及人类晕厥时的典型“翻白眼”症状，同时机体的心率、血压和呼吸率也会受到抑制。此外，研究人员还测定了流向大脑的血流量会减少。研究者总结道，当我们看到它们的眼睛在大脑活性迅速下降的同时翻了回去时，我们大吃一惊；几秒钟后，其机体大脑的活性和运动又恢复了过来。进一步研究表明，当NPY2R VSNs从小鼠机体移除后，BJR和晕厥症状就会消失。此前的研究结果表明，晕厥是由大脑血流量减少所引起的，而这项最新研究也发现的确如此，但最新研究证据表明，大脑活动本身或许扮演着重要角色，因此，相关研究认为，新型遗传识别的VSNs机器神经通路的激活不仅与BJR有关，更重要的是还与整个动物机体的生理学、某些大脑网络甚至行为有关。由于神经科学家们主要研究大脑，而心脏学家们主要研究心脏，所以此前研究人员很难梳理出这样的研究发现，而且许多研究都是分开进行的；研究者认为，从传统上来讲，神经科学家们认为身体只是跟着大脑走，但如今越来越多的研究都表明，机体会向大脑发送信号，随后大脑就会改变其功能。基于研究人员的最新发现，后期他们将会继续深入研究来追踪迷走神经感觉神经元被诱发开始行动背后的精确条件。研究者指出，他们还希望能更加仔细地分析在晕厥发生时机体大脑的脑血流量和神经回路，从而更好地理解这种常见但又神秘的情况。此外，研究人员还希望这一研究能作为一种模式帮助开发针对晕厥相关疾病的靶向性疗法。综上，本文研究结果阐明了一种遗传学定义的心脏反射机制，其在生理学、行为学和神经网络水平上都概括了人类晕厥发生的主要特征。原始出处：Jonathan W Lovelace,Jingrui Ma,Saurabh Yadav, et al. Vagal sensory neurons mediate the Bezold–Jarisch reflex and induce syncope, Nature (2023). DOI:10.1038/s41586-023-06680-7本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

2023-11-03

·生物谷

晚讯 |频繁使用手机与男性精子浓度和精子总数降低有关、中国国际杰青计划十周年已吸引 700 余名国际学者来华

1、中国国际杰青计划十周年：已吸引 700 余名国际学者来华11 月 1 日，科技部主办的国际杰青计划十周年研讨会上，记者获悉，截至 2023 年 8 月，国际杰青计划共吸引超过 40 个国家的青年科学家逾 700 人次到中国 20 多个省、自治区、直辖市的 200 余家单位工作学习，是参与国别最多、覆盖领域最广的中外科技人文交流机制之一。2、科学家发现控制晕厥的心脑神经通路无论是由于炎热、饥饿、站立时间过长，还是因为看到血或针头，40% 的人一生中至少会晕倒一次，这些短暂的意识丧失——晕厥——的具体机制一直是个谜。近日，美国加利福尼亚大学圣迭戈分校（UCSD）的研究团队发现了一组未被报道过的连接心脏和脑干的感觉神经元 NPY2R VSN，激活这些神经元会使小鼠迅速出现临床晕厥的表型，NPY2R VSN 和下丘脑室周带（periventricular zone）区域的神经网络共同调控着晕厥和随后的快速恢复。3、首个针对“超级淋病”的治疗方法通过试验11月1日，非营利组织全球抗生素研究与开发伙伴关系（GARDP）宣布，首个治疗“超级淋病”的新型抗生素在大规模临床试验中取得了良好效果。GARDP在11月1日发布的新闻稿中报告说，这些病例都不是由对头孢曲松或阿奇霉素耐药的细菌引起，但是试验发现唑利氟达星在治疗感染方面与这些药物一样有效。GARDP的执行主任Manica Balasegaram说，试验还发现唑利氟达星是安全的，参与者对它的耐受性很好。4、瑞斯凯尔完成超亿元B轮融资2023年11月3日，青岛瑞斯凯尔生物科技有限公司完成亿余元B轮融资，本轮融资由中信医疗基金领投，中金资本旗下基金、重庆一诺、巨峰科创等跟投。青岛瑞斯凯尔生物科技有限公司是一家以生命科学研究与体外诊断产品研发、生产、销售和服务为一体的高新技术企业。未来，瑞斯凯尔将永远不忘为人类健康事业发展而努力奋斗的初心，不断提升自身的创新能力，在新的更高的平台上砥砺前行。5、依诺基科完成近亿元Pre-A轮融资，用于生产基地建设等2023年11月3日，上海依诺基科生物技术有限公司宣布完成近亿元人民币Pre-A轮融资。本轮融资由丰川资本领投，信成基金、复容投资、景盛资本、开势诚形、怀济投资共同完成，融资款将主要用于生产基地建设、管线研发落地和人才团队的扩充。本轮融资也是依诺基科成立一年以来完成的第二轮融资。6、因美纳推出先进的液体活检检测产品，助力实体瘤的全景变异分析2023年11月1日，全球基因测序和芯片技术领导者因美纳公司宣布推出新一代液体活检基因组分析产品。全新的TruSight™ Oncology 500 ctDNA v2（TSO 500 ctDNA v2）是一项科研检测产品，可在组织检测不可行，或需要补充基于组织的测试时，对血液中的循环肿瘤DNA（ctDNA）进行无创全景变异分析（CGP）。该产品的革新之处包括：从样品到结果的周转时间更快（不到四天），灵敏度更高，对游离DNA（cfDNA）的起始量要求更低，工作流程也更为精简高效，并预计将在2024年上半年进一步实现自动化。7、频繁使用手机与男性精子浓度和精子总数降低有关当地时间 10 月 31 日，瑞士日内瓦大学（UNIGE）的科学家在《生育与不育》（Fertility & Sterility）杂志发表论文，称频繁使用手机与精子浓度和精子总数降低有关，并推测电磁波可能以某种方式影响了精液质量。该研究分析了 2886 名 18 至 22 岁的瑞士男性的精液质量，通过调查问卷询问他们的生活习惯和总体健康状况，特别是使用手机的频率以及不使用手机时手机的放置位置。结果表明，经常使用手机（>20 次/天）的男性的精子浓度（4450 万/毫升）比很少使用手机（<1 次/天）的男性的精子浓度（5650万/毫升）低 21%。不过，研究人员尚未发现使用手机与精子活力和形态的关联。此外，该研究还发现，与 2008-2011 年和 2012-2018 年的数据相比，精子质量在前一个阶段下降得更为剧烈，这与从 2G 过渡到 4G 相应的手机发射功率逐渐下降趋势相吻合。研究人员猜测电磁波在以某种方式影响精液质量，但由于研究对象中保持手机远离身体的人太少，因此无法得出可靠结论。本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！