更新于：2024-05-01

PKD2

polycystin 2, transient receptor potential cation channel

更新于：2024-05-01

基本信息

别名

Autosomal dominant polycystic kidney disease type II protein、Pc-2、PC2

+ [11]

简介

Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Can also form a functional, homotetrameric ion channel (PubMed:29899465). Functions as a cation channel involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (PubMed:18695040). Functions as outward-rectifying K(+) channel, but is also permeable to Ca(2+), and to a much lesser degree also to Na(+) (PubMed:11854751, PubMed:15692563, PubMed:27071085, PubMed:27991905). May contribute to the release of Ca(2+) stores from the endoplasmic reticulum (PubMed:11854751, PubMed:20881056). Together with TRPV4, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). PKD1 and PKD2 may function through a common signaling pathway that is necessary to maintain the normal, differentiated state of renal tubule cells. Acts as a regulator of cilium length, together with PKD1. The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling. Also involved in left-right axis specification via its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to facilitate flow detection in left-right patterning. Detection of asymmetric nodal flow gives rise to a Ca(2+) signal that is required for normal, asymmetric expression of genes involved in the specification of body left-right laterality (By similarity).

关联

100 项与 PKD2 相关的临床结果

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100 项与 PKD2 相关的转化医学

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0 项与 PKD2 相关的专利（医药）

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项与 PKD2 相关的文献（医药）

2024-02-24·Microbial cell factories

A genome-reduced Corynebacterium glutamicum derivative discloses a hidden pathway relevant for 1,2-propanediol production.

Article

作者: Daniel Siebert ; Erich Glawischnig ; Marie-Theres Wirth ; Mieke Vannahme ; Álvaro Salazar-Quirós ; Annette Weiske ; Ezgi Saydam ; Dominik Möggenried ; Volker F Wendisch ; Bastian Blombach

BACKGROUND:

1,2-propanediol (1,2-PDO) is widely used in the cosmetic, food, and drug industries with a worldwide consumption of over 1.5 million metric tons per year. Although efforts have been made to engineer microbial hosts such as Corynebacterium glutamicum to produce 1,2-PDO from renewable resources, the performance of such strains is still improvable to be competitive with existing petrochemical production routes.

RESULTS:

In this study, we enabled 1,2-PDO production in the genome-reduced strain C. glutamicum PC2 by introducing previously described modifications. The resulting strain showed reduced product formation but secreted 50 ± 1 mM D-lactate as byproduct. C. glutamicum PC2 lacks the D-lactate dehydrogenase which pointed to a yet unknown pathway relevant for 1,2-PDO production. Further analysis indicated that in C. glutamicum methylglyoxal, the precursor for 1,2-PDO synthesis, is detoxified with the antioxidant native mycothiol (MSH) by a glyoxalase-like system to lactoylmycothiol and converted to D-lactate which is rerouted into the central carbon metabolism at the level of pyruvate. Metabolomics of cell extracts of the empty vector-carrying wildtype, a 1,2-PDO producer and its derivative with inactive D-lactate dehydrogenase identified major mass peaks characteristic for lactoylmycothiol and its precursors MSH and glucosaminyl-myo-inositol, whereas the respective mass peaks were absent in a production strain with inactivated MSH synthesis. Deletion of mshA, encoding MSH synthase, in the 1,2-PDO producing strain C. glutamicum ΔhdpAΔldh(pEKEx3-mgsA-yqhD-gldA) improved the product yield by 56% to 0.53 ± 0.01 mM_1,2-PDO mM_glucose^-1 which is the highest value for C. glutamicum reported so far.

CONCLUSIONS:

Genome reduced-strains are a useful basis to unravel metabolic constraints for strain engineering and disclosed in this study the pathway to detoxify methylglyoxal which represents a precursor for 1,2-PDO production. Subsequent inactivation of the competing pathway significantly improved the 1,2-PDO yield.

2024-02-16·iScience

Protein kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines.

Article

作者: Alexia Gali ; Irene V Bijnsdorp ; Sander R Piersma ; Thang V Pham ; Elena Gutiérrez-Galindo ; Fiona Kühnel ; Nikos Tsolakos ; Connie R Jimenez ; Angelika Hausser ; Leonidas G Alexopoulos

The protein kinase D (PKD) family members regulate the fission of cargo vesicles at the Golgi complex and play a pro-oncogenic role in triple-negative breast cancer (TNBC). Whether PKD facilitates the secretion of tumor-promoting factors in TNBC, however, is still unknown. Using the pharmacological inhibition of PKD activity and siRNA-mediated depletion of PKD2 and PKD3, we identified the PKD-dependent secretome of the TNBC cell lines MDA-MB-231 and MDA-MB-468. Mass spectrometry-based proteomics and antibody-based assays revealed a significant downregulation of extracellular matrix related proteins and pro-invasive factors such as LIF, MMP-1, MMP-13, IL-11, M-CSF and GM-CSF in PKD-perturbed cells. Notably, secretion of these proteins in MDA-MB-231 cells was predominantly controlled by PKD2 and enhanced spheroid invasion. Consistently, PKD-dependent secretion of pro-invasive factors was more pronounced in metastatic TNBC cell lines. Our study thus uncovers a novel role of PKD2 in releasing a pro-invasive secretome.

2024-02-14·Scientific reports

Changes of physicochemical and functional properties of processed cheese made with natural cheddar and mozzarella cheeses during refrigerated storage.

Article

作者: Tongji Liu ; Jingwei Wu ; Tariq Aziz ; Rui Xue ; Manal M Khowdiary ; Zhennai Yang

The present study aimed to investigate changes of physicochemical and functional properties of the processed cheeses (PCs) made with Cheddar (PC1), Mozzarella (PC2) and both of them at a ratio of 1:1 (PC3) during storage at 4 °C for 4 months. The results showed that the type of natural cheese used affected the composition of PCs with lower fat content in PC2 due to the lower fat content of Mozzarella cheese used. PC2 with lower fat content showed decreased meltability and oil leakage compared with PC1 and PC3. The stretchability of all the samples significantly (P < 0.05) decreased during storage, and PC1 showed lower stretchability. This was confirmed by increased protein hydrolysis of all the samples during the storage with a higher level of proteolysis in PC1, leading to decreased stretchability of PCs. Further low-field nuclear magnetic resonance analysis indicated more entrapped water in cheese due to moisture migration into the cheese matrix that might squeeze the fat globules to aggregate, causing more fat leakage during later stages of storage. This was evidenced by microstructural analysis showing different extents of increase in fat particle sizes and decrease in free serum in all the PC samples over the storage time. Therefore, the present study provides further understanding of the mechanism of quality change of PC during refrigerated storage as affected by proteolytic properties and composition of natural cheese used.

项与 PKD2 相关的新闻（医药）

2024-03-31

·医药观澜

礼邦医药在研新药获FDA授予孤儿药资格，针对肾病！

▎药明康德内容团队编辑3月29日，礼邦医药宣布其在研创新药物AP303获得美国FDA授予孤儿药资格，用于治疗常染色体显性多囊肾病（ADPKD）。ADPKD是常见的单基因肾病，也是导致成人终末期肾病的主要原因之一。该病的主要表现为肾脏囊肿不断增大、增多，破坏正常的肾脏结构和功能。ADPKD最常见的致病原因有两个：一是多囊肾致病基因PKD1突变，约存在78%的疾病谱系中；二是PKD2突变，约存在15%的疾病谱系中。对于ADPKD患者的治疗，临床上建议包括抗高血压治疗、饮食限制以及仅适合部分患者的药物治疗。目前，ADPKD患者迫切需要可治疗更多患者且副作用更少的有效治疗药物，以减缓患者的肾功能衰退并改善肾脏结局。AP303是礼邦医药自主研发的一款创新药物。在ADPKD小鼠模型中，已观察到肾脏存活率提高。目前该药已完成其在健康受试者中的首次人体试验，并准备进行针对ADPKD的2期临床研究。礼邦医药成立于2018年初，致力于肾脏病以及其它相关慢性疾病创新药物的发现和开发，为慢性肾脏病及相关疾病患者提供更佳的临床治疗方案。目前，该公司已建立起包含多款肾脏病新药的产品管线，拟开发适应症涵盖慢性肾病/透析并发症、IgA肾病、糖尿病肾病、常染色体显性多囊肾病等产品。参考资料：[1]礼邦医药在研创新药物 AP303 获得美国食品药品监督管理局孤儿药资格认定, 用于治疗常染色体显性多囊肾病（ADPKD）. Retrieved Mar 29 , 2024, from https://mp.weixin.qq.com/s/LqsGIoaCQ_zKvPxDulcqVA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。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。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。

孤儿药临床2期快速通道

2024-03-29

·医药魔方Pro

礼邦医药：创新药AP303获FDA孤儿药资格认定，治疗常染色体显性多囊肾病

2024 年 3 月 29 日，礼邦医药宣布其在研创新药物 AP303 获得美国食品药品监督管理局（FDA）孤儿药资格认定，用于治疗常染色体显性多囊肾病（ADPKD）。ADPKD是最常见的单基因肾病，也是全球导致成人终末期肾病的主要原因之一，主要表现为肾脏囊肿不断增大、增多，破坏正常的肾脏结构和功能。ADPKD 最常见的原因是多囊肾致病基因PKD1（在78%的疾病谱系中）或 PKD2（在15%的疾病谱系中）突变。对于ADPKD患者的治疗建议包括抗高血压治疗、饮食限制以及仅适合部分患者的药物治疗。ADPKD患者迫切需要可治疗更多患者且副作用更少的有效治疗药物以减缓患者的肾功能衰退并改善肾脏结局。AP303是礼邦医药自主研发的创新药物，在ADPKD小鼠模型中观察到肾脏存活率的提高, 并已完成在健康受试者中的首次人体试验，即将进行II期临床研究。ADPKD 在新生儿中的患病率约为四百分之一到千分之一，该疾病是导致终末期肾病（ESKD）需接受肾脏替代治疗的重要原因[1]。此次孤儿药认定显示出治疗 ADPKD 的迫切临床需求，以及 AP303 未来为患者提供更多治疗手段的潜力。“我们非常高兴 AP303 被 FDA 授予孤儿药资格。”礼邦医药联合创始人、董事长兼首席执行官夏国尧博士评论道，“这对于礼邦医药以及我们为解决 ADPKD 疾病未满足的临床需求所做的努力而言都是一个重要里程碑。我们会努力推进AP303 项目，为 ADPKD 患者提供更多的治疗选择。”2018 年初，礼邦医药由顶尖的肾脏病领域行业领导者孵化于中国上海，主要致力于肾脏病以及其他相关慢性疾病创新药物的发现和开发，为慢性肾脏病及相关疾病患者提供更佳临床治疗方案。礼邦医药已经建立起了丰富且均衡的肾脏病新药产品管线，包括针对慢性肾病（CKD）/透析并发症、IgA 肾病、糖尿病肾病、常染色体显性多囊肾病（ADPKD）等产品，公司在研产品包括小分子药物和生物制剂，目前多个项目处于临床试验阶段。参考文献：[1]Bergmann, C., Guay-Woodford, L.M., Harris, P.C. et al. Polycystic kidney disease. Nat Rev Dis Primers 4, 50 (2018). https://doi.org/10.1038/s41572-018-0047-yCopyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

孤儿药

2024-03-29

·PRNewswire

Alebund's Innovative Investigational Drug AP303 Receives FDA Orphan Drug Designation (ODD) for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

SHANGHAI, March 29, 2024 /PRNewswire/ -- Alebund Pharmaceuticals ("Alebund" or the "Company"), an integrated biopharmaceutical company focusing on developing innovative therapies for the treatment of renal diseases and related chronic conditions, announced today that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to AP303 for the treatment of autosomal dominant polycystic kidney disease (ADPKD). "We are very excited that AP303 has been granted Orphan Drug Designation by the FDA", Dr. Gavin Xia, Co-founder, Chairman, and CEO of Alebund commented. "It is an important milestone for Alebund as well as our efforts to address the significant unmet medical needs with ADPKD. We look forward to advancing AP303 to improve future treatment options for patients in need." AP303, a novel drug candidate developed in-house by Alebund, has demonstrated a meaningful improvement of renal survival in an ADPKD mice model. AP303 has completed its first-in-human study in healthy subjects in Australia and is ready for a Phase II trial in ADPKD. The prevalence of ADPKD is reported to be between 1 in 400 and 1 in 1,000 live births; it is an important cause of end-stage kidney disease (ESKD) requiring renal replacement therapy [1]. This Orphan Drug Designation reflects the need for more new treatment options and the potential for AP303 to address the pressing needs of people living with ADPKD. The US FDA's ODD is a special status granted to support the development and evaluation of potential new medicines intended for the treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US. The designation provides incentives to advance the development of treatments for rare diseases, including marketing exclusivity, tax credits for clinical research costs, and exemption from prescription drug user fees. About ADPKD ADPKD is the most common monogenic kidney disease and one of the leading causes of end-stage kidney disease in adults worldwide. Its course is characterized by the development and inexorable expansion of multiple cysts scattered throughout the kidney parenchyma. ADPKD is most caused by mutations in the genes PKD1 (in 78% of disease pedigrees) or PKD2 (in 15% of disease pedigrees). Treatment recommendation for patients with ADPKD includes anti-hypertensive treatment, dietary restrictions, and pharmacotherapy for a limited percentage of suitable patients. More broadly applicable treatment options with fewer side effects are needed to effectively slow the decline of kidney function and improve kidney outcomes in patients with ADPKD. About Alebund Pharmaceuticals Alebund is a biopharmaceutical company jointly incubated by a group of industry leaders in the field of nephrology in Shanghai in 2018. Alebund focuses on the discovery and development of novel therapies primarily for kidney diseases and their complications, as well as other chronic conditions. Alebund has built a diversified and balanced pipeline of drug candidates targeting a range of renal diseases, including chronic kidney disease (CKD)/dialysis complications, IgA nephropathy, diabetic kidney disease, and autosomal dominant polycystic kidney disease (ADPKD). Alebund's pipeline comprises both small-molecule and biological assets, in which many programs are in the clinical stage. [1] Bergmann, C., Guay-Woodford, L.M., Harris, P.C. et al. Polycystic kidney disease. Nat Rev Dis Primers 4, 50 (2018). SOURCE Alebund Pharmaceuticals

孤儿药临床2期