更新于：2024-11-01

PLXNA1

更新于：2024-11-01

基本信息

别名

NOV、plexin A1、Plexin-A1

+ [3]

简介

Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm (By similarity).

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100 项与 PLXNA1 相关的临床结果

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100 项与 PLXNA1 相关的转化医学

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0 项与 PLXNA1 相关的专利（医药）

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189

项与 PLXNA1 相关的文献（医药）

2024-11-01·Neoplasia

PLXNA1 confers enzalutamide resistance in prostate cancer via AKT signaling pathway

Article

作者: Han, Bo ; Zhang, Qian ; Yu, Zeyuan ; Sun, Feifei ; Zhang, Lin ; Zhang, Jing ; Hu, Jing ; Dou, Baokai ; Chen, Weiwen ; Feng, Tingting ; Han, Jingying ; Gao, Lin ; Liu, Hui ; Qu, Ying

Although targeting the androgen signaling pathway by androgen receptor (AR) inhibitors, including enzalutamide, has shown therapeutic effectiveness, inevitable emergence of acquired resistance remains a critical challenge in the treatment of advanced prostate cancer (PCa). Recognizing targetable genomic aberrations that trigger endocrine treatment failure holds great promise for advancing therapeutic interventions. Here, we characterized PLXNA1, amplified in a subset of PCa patients, as a contributor to enzalutamide resistance (ENZR). Elevated PLXNA1 expression facilitated PCa proliferation under enzalutamide treatment due to AKT signaling activation. Mechanistically, PLXNA1 recruited NRP1 forming a PLXNA1-NRP1 complex, which in turn potentiated the phosphorylation of the AKT. Either inhibiting PLXNA1-NRP1 complex with an NRP1 inhibitor, EG01377, or targeting PLXNA1-mediated ENZR with AKT inhibitors, abolished the pro-resistance phenotype of PLXNA1. Taken together, combination of AKT inhibitor and AR inhibitors presents a promising therapeutic strategy for PCa, especially in advanced PCa patients exhibiting PLXNA1 overexpression.

2024-07-01·Journal of Medical Genetics

Biallelic variants in Plexin B2 ( PLXNB2 ) cause amelogenesis imperfecta, hearing loss and intellectual disability

Article

作者: Rigby, Alice ; Watson, Christopher M ; Mayr, Johannes A ; Black, Graeme C ; Smith, Claire E L ; Inglehearn, Chris F ; Nikolopoulos, Georgios ; Poulter, James A ; Mansour, Sahar ; Taylor, Rachel L ; Best, Sunayna ; Wortmann, Saskia B ; Feichtinger, Rene G ; Bloch-Zupan, Agnès ; Hany, Ummey ; Mighell, Alan J ; Laugel-Haushalter, Virginie ; Al Bahlani, Suhaila

Background Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Nine plexin genes have been identified in humans, but despite the apparent importance of plexins in development, only biallelic PLXND1 and PLXNA1 variants have so far been associated with Mendelian genetic disease. MethodsEight individuals from six families presented with a recessively inherited variable clinical condition, with core features of amelogenesis imperfecta (AI) and sensorineural hearing loss (SNHL), with variable intellectual disability. Probands were investigated by exome or genome sequencing. Common variants and those unlikely to affect function were excluded. Variants consistent with autosomal recessive inheritance were prioritised. Variant segregation analysis was performed by Sanger sequencing. RNA expression analysis was conducted in C57Bl6 mice.Results Rare biallelic pathogenic variants in plexin B2 ( PLXNB2 ), a large transmembrane semaphorin receptor protein, were found to segregate with disease in all six families. The variants identified include missense, nonsense, splicing changes and a multiexon deletion. Plxnb2 expression was detected in differentiating ameloblasts. Conclusion We identify rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and SNHL as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. The variable syndromic human phenotype overlaps with that seen in Plxnb2 knockout mice, and, together with the rarity of human PLXNB2 variants, may explain why pathogenic variants in PLXNB2 have not been reported previously.

2024-06-01·Molecular Neurobiology

Lowering Hippocampal miR-29a Expression Slows Cognitive Decline and Reduces Beta-Amyloid Deposition in 5×FAD Mice

Article

作者: Liu, Jiaqi ; Duong, Duc M ; Schroeder, Jason P ; Jin, Peng ; Mei, Zhen ; Wingo, Thomas S ; Wingo, Aliza P ; Weinshenker, David ; Li, Yujing ; Seyfried, Nicholas T

AbstractmicroRNA-29a (miR-29a) increases with age in humans and mice, and, in the brain, it has a role in neuronal maturation and response to inflammation. We previously found higher miR-29a levels in the human brain to be associated with faster antemortem cognitive decline, suggesting that lowering miR-29a levels could ameliorate memory impairment in the 5×FAD AD mouse model. To test this, we generated an adeno-associated virus (AAV) expressing GFP and a miR-29a “sponge” or empty vector. We found that the AAV expressing miR-29a sponge functionally reduced miR-29a levels and improved measures of memory in the Morris water maze and fear condition paradigms when delivered to the hippocampi of 5×FAD and WT mice. miR-29a sponge significantly reduced hippocampal beta-amyloid deposition in 5×FAD mice and lowered astrocyte and microglia activation in both 5×FAD and WT mice. Using transcriptomic and proteomic sequencing, we identified Plxna1 and Wdfy1 as putative effectors at the transcript and protein level in WT and 5×FAD mice, respectively. These data indicate that lower miR-29a levels mitigate cognitive decline, making miR-29a and its target genes worth further evaluation as targets to mitigate Alzheimer’s disease (AD).

项与 PLXNA1 相关的新闻（医药）

2024-10-21

·PRNewswire

Find Therapeutics Announces First Subject Dosed in Phase 1 Clinical Study of FTX-101

MONTREAL, Oct. 21, 2024 /PRNewswire/ - Find Therapeutics Inc., a clinical-stage biopharmaceutical company focused on the development of innovative therapies for autoimmune diseases, today announced initiation of dosing in its Phase 1 clinical study of FTX-101 in healthy volunteers. FTX-101 is a first-in-class therapeutic peptide that modulates the Plexin A1 / Neuropilin 1 transmembrane receptor complex in the brain to promote remyelination. Following completion of the Phase 1 clincal study, Find plans to investigate the use of FTX-101 in individuals with Chronic Optic Neuropathy – a long-term condition due to demyelination in the visual tracts of the brain and optic nerve, with serious effects on visual acuity and perception. The Phase 1 first-in-human study will assess the safety, tolerability, and pharmacokinetics of FTX-101 when administered in healthy volunteers. The study is being initiated after the US Food and Drug Administration authorized initiation of the study earlier this year. The clinical study consists of two parts. Part 1 is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study comprised of 40 subjects receiving FTX-101 or placebo while Part 2 is a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study that will enroll 24 subjects receiving FTX-101 or placebo. "The initiation of this study is a significant milestone for both our company and individuals who suffer with Chronic Optic Neuropathy," said Philippe Douville, CEO of Find. "In this study, we will build on the large body of preclinical evidence demonstrating FTX-101's effects in models of autoimmune disease. A therapy of this type would represent a major step forward in finding the first treatment to improve the lives of people afflicted with Chronic Optic Neuropathy. We look forward to sharing data from this study in the first half of 2025." About FTX-101 Find's lead compound, FTX-101, is a first-in-class remyelinating agent that aims to restore vision to people suffering from Chronic Optic Neuropathy. FTX-101 is a rationally designed therapeutic peptide that targets Plexin A1 and Neuropilin 1, a receptor complex present in the brain that has been shown to be involved in the migration and differentiation of oligodendrocyte precursor cells into myelinating oligodendrocytes. Compelling preclinical data for FTX-101 in demyelinating models show strong myelin repair activity. About Find Find Therapeutics is clinical-stage biopharmaceutical company dedicated to the development of next generation therapies to treat inflammatory autoimmune diseases. The company was launched in 2020 and is supported with investments from CTI Life Sciences, adMare BioInnovations, Domain Therapeutics and Investissment Québec and an exclusive license from SATT-Conectus and the University of Strasbourg on a technology and related know-how. Visit for more details about Find Therapeutics. SOURCE Find Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期引进/卖出

2024-09-16

·PRNewswire

Find Therapeutics Announces the Closing of a Convertible Note Financing with Investissement Québec

$8.1 million convertible note financing by Investissement Québec and current investors CTI Life Sciences Fund and adMare BioInnovations MONTREAL, Sept. 16, 2024 /PRNewswire/ - Find Therapeutics Inc., a biopharmaceutical company focused on the development of innovative therapies for autoimmune diseases, today announced the closing of a $8.1 million (CAD$11 million) convertible note financing led by Investissement Québec with participation from current investors CTI Life Sciences Fund and adMare BioInnovations. The proceeds of the convertible note will be used to advance FTX-101 into Phase 1 clinical studies. "We are excited to welcome Investissement Québec as a new investor in Find," said Philippe Douville, CEO of Find. "With the recent clearance of the IND by the FDA and this new investment by Investissement Québec and our current investors, we are able to accelerate FTX-101 into the clinic to bring a much-needed myelin repair therapy to patients." The Phase 1 clinical trial is anticipated to commence in Q4 2024 and is designed to evaluate safety, tolerability, and pharmacokinetics of FTX-101 across different dose levels in healthy volunteers. "Investissement Québec is proud to assist Find Therapeutics in its innovation and development efforts and to help fill a gap in the capital chain for young biotech businesses," said Bicha Ngo, President and CEO of Investissement Québec. "Through our support for the company, we are contributing to the launch of its clinical studies and enabling it to deliver on the next phases of growth, with the ultimate aim of promoting better visual health." About FTX-101 Find's lead compound, FTX-101, is a first-in-class remyelinating agent that aims to restore vision in people suffering from Chronic Optic Neuropathy (CON). FTX-101 is a rationally designed therapeutic peptide that targets Plexin A1 and Neuropilin 1, a receptor complex present in the brain that has been shown to be involved in the migration and differentiation of oligodendrocyte precursor cells into myelinating oligodendrocytes. Compelling preclinical data for FTX-101 in demyelinating models show strong myelin repair activity. About Investissement Québec Investissement Québec's mission is to play an active role in Quebec's economic development by stimulating business innovation, entrepreneurship, and business acquisitions, as well as growth in investment and exports. Operating in all the province's administrative regions, the Corporation supports the creation and growth of businesses of all sizes with investments and customized financial solutions. It also assists businesses by providing consulting services and other support measures, including technological assistance available from Investissement Québec Innovation. In addition, through Investissement Québec International, the Corporation prospects for talent and foreign investment, and assists Quebec businesses with export activities. About Find Find Therapeutics is dedicated to the development of next generation therapies to treat inflammatory autoimmune diseases. The company was launched in 2020 with investments from CTI Life Sciences, adMare BioInnovations and Domain Therapeutics and an exclusive license from Strasbourg University on a technology and related know-how initially developed by Dr. Dominique Bagnard. Visit for more details about Find Therapeutics. SOURCE Find Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期引进/卖出临床申请

2024-09-02

·药明康德

穿越血脑屏障的变构小分子疗法早期结果积极；使化疗耐药患者肿瘤完全消失的靶向疗法将启动新研究…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 盐诱导激酶（SIK）抑制剂OMX-0407在1a期临床试验中使1名对多种化疗药物耐药的晚期实体瘤患者的肿瘤完全消失。 2. 治疗帕金森病的变构小分子疗法GT-02287的早期临床结果积极，它能够穿越血脑屏障并与靶标结合，同时展现良好的安全性与耐受性。药明康德内容团队整理 OMX-0407：公布1a期临床试验数据 iOmx Therapeutics公司宣布，其潜在“first-in-class”的选择性SIK抑制剂OMX-0407的1a期临床试验已顺利完成，即将启动1b期临床试验。OMX-0407能够通过调控酪氨酸激酶信号直接干扰肿瘤细胞增殖。除了这种直接作用方式外，OMX-0407还能通过增强肿瘤坏死因子等死亡受体配体引发的肿瘤细胞凋亡，重塑肿瘤微环境。初步数据显示，OMX-0407单药治疗是安全且耐受性良好的。OMX-0407对经过多次治疗的晚期实体瘤患者有抗癌活性。其中，一名对多种化疗药物耐药的患者达到了持久的完全缓解（CR），所有肿瘤病灶均消失。此外，生物标志物分析表明，循环血细胞中存在确凿的药理活性证据。 GT-02287：公布1期临床试验数据 Gain Therapeutics宣布其用于治疗帕金森病的在研变构小分子GT-02287在1期试验中获得积极结果。GT-02287是一种口服变构蛋白调节剂，具有可穿越血脑屏障的小分子量。该药物可恢复溶酶体蛋白酶葡萄糖脑苷脂酶（GCase）的功能，该酶由于GBA1基因突变（与帕金森病相关的最常见遗传异常）或其他与年龄相关的压力因素而发生错误折叠和受损。在帕金森病的临床前模型中，GT-02287恢复了GCase酶功能，减少了聚集的α突触核蛋白、神经炎症和神经元死亡，提高了多巴胺水平，改善动物的运动功能和认知能力，可能具有减缓帕金森病进展的潜力。此外，GT-02287显著降低了血浆神经丝轻链（NfL）水平，这是一种神经退行性疾病的生物标志物。此次公布的结果显示，GT-02287存在于受试者的脑脊液中，并与外周靶标相结合。在具良好安全性与耐受性的口服剂量下，该药物的血浆水平达到治疗性水平，并可抵达中枢神经系统并与靶标相结合，显示GT-02287是潜在的帕金森病疗法，无论患者是否具有GBA1突变。Gain Therapeutics预计在今年第四季度启动该疗法的1b期临床试验。 Exidavnemab：公布1期临床试验数据 BioArctic公司公布了其靶向聚集的α突触核蛋白的单克隆抗体exidavnemab的两项与艾伯维合作开展的1期研究的积极结果。该候选药物旨在治疗帕金森病等神经退行性疾病。结果显示，85名接受了exidavnemab静脉注射或皮下注射的受试者对治疗的总体耐受性良好。Exidavnemab的半衰期约30天，对聚集的α突触核蛋白具有高亲和力和选择性，这是其在大脑中保持高靶点结合力的关键。 OCU410ST：1/2期临床试验完成第三个队列的给药 Ocugen公司宣布，其针对Stargardt病开发的候选基因疗法OCU410ST的1/2期临床试验已完成第三个队列的给药。OCU410ST利用腺相关病毒（AAV）递送平台在视网膜递送RORA基因，可调节与Stargardt病相关的通路，例如脂褐素形成、氧化应激、炎症、细胞存活网络等。 FTX-101：IND申请获得FDA许可 Find Therapeutics公司宣布，美国FDA已经批准了FTX-101的IND申请，该公司计划在2024年第四季度启动FTX-101在健康志愿者中的1期临床研究。FTX-101是一种潜在“first-in-class”的髓鞘再生剂，旨在恢复慢性视神经病变患者的视力。FTX-101是一种经过合理设计的治疗肽，靶向Plexin A1和Neuropilin 1。Plexin A1和Neuropilin 1是大脑中存在的一种受体复合物，已被证明参与了少突胶质细胞前体细胞迁移和分化成髓鞘化少突胶质细胞的过程。临床前数据显示，FTX-101在脱髓鞘模型中具有很强的髓鞘修复活性。 ID110521156：IND申请获得韩国食品药品安全部许可 Yunovia公司宣布，韩国食品药品安全部（MFDS）已批准其口服的小分子GLP-1受体激动剂ID110521156用于治疗糖尿病和肥胖的IND申请，可启动1期多剂量递增（MAD）研究。ID110521156具有与GLP-1激素相同的作用，包括促进体内胰岛素的合成和分泌、降低血糖水平、调节胃肠道运动以及抑制食欲。作为一款小分子疗法，ID110521156与当前的标准治疗肽类注射剂相比，具有制造方便和使用简便等差异化特性。 Yunovia已于2024年7月完成了ID110521156的1期单剂量递增研究，包括食物效应研究。结果显示，ID110521156的耐受性良好，有望作为一种每日一次疗法。 MB097、MB310：获批在欧盟和英国启动1b期临床试验 Microbiotica公司宣布，其开发的两款活体生物治疗产品（LBP）MB097和MB310已获得监管部门的批准，可以在选定的欧盟国家和英国启动临床研究。MB097是一种每日一次的口服LBP，由九种细菌菌株组成，能够提供免疫检查点抑制剂（ICI）反应所需的微生物组信号，旨在提高ICI的疗效。临床前研究表明，MB097能够刺激免疫系统的核心途径，激活细胞毒性T淋巴细胞和自然杀伤细胞，使其能够杀死肿瘤细胞。此次开展的1b期研究将评估MB097联用PD-1抑制剂pembrolizumab治疗晚期黑色素瘤的安全性和疗效。 MB310是从健康供体中鉴定出的一个明确的微生物群落。临床前研究表明，MB310能够通过至少三种独立的机制发挥对溃疡性结肠炎的治疗作用，包括促进受损肠道上皮屏障的愈合，调节炎症和免疫调节细胞因子的平衡，以及诱导调节性T细胞反应。此次开展的1b期研究将评估MB310治疗溃疡性结肠炎的安全性和疗效。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Ocugen Announces Completion of Dosing in Subjects with Stargardt Disease in High Dose Cohort of Phase 1/2 GARDian Clinical Trial of OCU410ST—A Modifier Gene Therapy. Retrieved August 30, 2024, from https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-completion-dosing-subjects-stargardt-disease [2] Study results from phase 1 studies with exidavnemab published in The Journal of Clinical Pharmacology. Retrieved August 30, 2024, from https://www.prnewswire.com/news-releases/study-results-from-phase-1-studies-with-exidavnemab-published-in-the-journal-of-clinical-pharmacology-302231302.html [3] Find Therapeutics Announces FDA Clearance of IND Application for a Phase 1 Study of FTX-101 for the Treatment of Chronic Optic Neuropathy. Retrieved August 30, 2024, from https://www.prnewswire.com/news-releases/find-therapeutics-announces-fda-clearance-of-ind-application-for-a-phase-1-study-of-ftx-101-for-the-treatment-of-chronic-optic-neuropathy-302229869.html [4] Gain Therapeutics Announces Positive Topline Results from the Phase 1 Clinical Trial of GT-02287, a Novel GCase-Targeting Small Molecule Therapy for Parkinson’s Disease. Retrieved August 29, 2024, from https://www.gaintherapeutics.com/newsroom/press-releases/press-releases-2024/ainherapeuticsnnouncesositiveoplineesultsfromth20240829043502 [5] iOmx Therapeutics Initiates Phase Ib with OMX-0407. Retrieved August 30, 2024, from https://www.globenewswire.com/en/news-release/2024/08/22/2933999/0/en/iOmx-Therapeutics-Initiates-Phase-Ib-with-OMX-0407.html [6] AiViva Biopharma Completes Enrollment in a Phase 1 Clinical Trial of AIV007 for Age-Related Macular Degeneration and Diabetic Macular Edema. Retrieved August 30, 2024, from https://aiviva.com/2024/08/aiviva-biopharma-completes-enrollment-in-a-phase-1-clinical-trial-of-aiv007-for-age-related-macular-degeneration-and-diabetic-macular-edema/ [7] First Patient Dosed with LIXTE’s LB-100 in New Clinical Trial to Treat Colorectal Cancer, Collaborating with NKI, Supported by Major Pharma Company. Retrieved August 30, 2024, from https://ir.lixte.com/news-events/press-releases/detail/115/first-patient-dosed-with-lixtes-lb-100-in-new-clinical-trial-to-treat-colorectal-cancer-collaborating-with-nki-supported-by-major-pharma-company [8] ENA Respiratory Progresses Phase Ib Study of its Dry Powder Formulation of Intranasal Innate Immunomodulator INNA-051. Retrieved August 30, 2024, from https://www.globenewswire.com/news-release/2024/08/27/2935974/0/en/ENA-Respiratory-Progresses-Phase-Ib-Study-of-its-Dry-Powder-Formulation-of-Intranasal-Innate-Immunomodulator-INNA-051.html [9] Yunovia Announces IND Approval by the MFDS to Initiate Phase 1 MAD Study for the Small Molecule GLP-1 Agonist. Retrieved August 30, 2024, from https://www.prnewswire.com/news-releases/yunovia-announces-ind-approval-by-the-mfds-to-initiate-phase-1-mad-study-for-the-small-molecule-glp-1-agonist-302232393.html [10] Microbiotica’s Microbiome Medicines in Melanoma and Ulcerative Colitis Gain Regulatory Approvals in EU and UK for Phase 1b Studies. Retrieved August 30, 2024, from https://www.globenewswire.com/news-release/2024/08/27/2935969/0/en/Microbiotica-s-Microbiome-Medicines-in-Melanoma-and-Ulcerative-Colitis-Gain-Regulatory-Approvals-in-EU-and-UK-for-Phase-1b-Studies.html 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：本文来自药明康德内容团队，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载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床1期临床结果临床2期