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更新于：2025-05-07

PDE9A

更新于：2025-05-07

基本信息

别名

High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A、PDE9A、phosphodiesterase 9A

简介

Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP (PubMed:18757755, PubMed:21483814, PubMed:9624146). Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart (PubMed:25799991). Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (Probable). In brain, involved in cognitive function, such as learning and long-term memory (By similarity).

关联

项与 PDE9A 相关的药物

E-2027

靶点

PDE9A

作用机制

PDE9A抑制剂

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3期

首次获批国家/地区-

首次获批日期1800-01-20

Tovinontrine

靶点

PDE9A

作用机制

PDE9A抑制剂

在研机构

Cardurion Pharmaceuticals, Inc.

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

CRD-740

靶点

PDE9A

作用机制

PDE9A抑制剂

在研机构

Cardurion Pharmaceuticals, Inc.

原研机构

Cardurion Pharmaceuticals, Inc.

在研适应症

心脏衰竭

非在研适应症

慢性心力衰竭 [+2]

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 PDE9A 相关的临床试验

CTIS2023-508736-62-00

/ Recruiting临床2期

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Finding Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Reduced Ejection Fraction - CRD-750-201

开始日期2024-08-19

申办/合作机构

Cardurion Pharmaceuticals, Inc.

NCT06215911

/ Recruiting临床2期

The purpose of this study is to evaluate the safety and effectiveness of tovinontrine compared to placebo to lower NT-proBNP in patients with chronic heart failure with reduced ejection fraction.

开始日期2024-02-13

申办/合作机构

Cardurion Pharmaceuticals, Inc.

NCT06215586

/ Recruiting临床2期

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess the Safety and Effectiveness of Tovinontrine in Patients With Chronic Heart Failure With Preserved Ejection Fraction

The purpose of this study is to evaluate the safety and effectiveness of tovinontrine compared to placebo to lower NT-proBNP in patients with chronic heart failure with preserved ejection fraction

开始日期2024-02-13

申办/合作机构

Cardurion Pharmaceuticals, Inc.

100 项与 PDE9A 相关的临床结果

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100 项与 PDE9A 相关的转化医学

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0 项与 PDE9A 相关的专利（医药）

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113

项与 PDE9A 相关的文献（医药）

2024-12-01·Animal Bioscience

Investigation of single nucleotide polymorphisms in differentially expressed genes and proteins reveals the genetic basis of skeletal muscle growth differences between Tibetan and Large White pigs

Article

作者: Xiong, Heli ; Zhang, Yan ; Zhao, Zhiyong

Objective: Skeletal muscle growth is an important economic trait for meat production, with notable differences between Tibetan pigs (TIBPs, a slow-growing breed) and Large White pigs (LWPs, a fast-growing breed). However, the genetic underpinnings of this disparity remain unclear.Methods: In the current study, we integrated differentially expressed genes (DEGs) and proteins (DEPs) from 60-day-old embryonic muscle tissue, along with whole-genome single nucleotide polymorphisms (SNPs) displaying absolute allele frequency differences (ΔAF) of 0.5 or more between the TIBP and LWP breeds, to unravel the genetic factors influencing skeletal muscle growth.Results: Our analysis revealed 3,499 DEGs and 628 DEPs with SNPs having a ΔAF equal to or greater than 0.5. Further functional analysis identified 145 DEGs and 23 DEPs involved in biological processes related to skeletal muscle development, and 22 DEGs and 3 DEPs implicated in the mechanistic target of rapamycin kinase signaling pathway, which is known for positively regulating protein synthesis. Among these genes, several DEGs and DEPs, enriched with TIPB-specific SNPs in regulatory or/and coding regions, showed marked ΔAF between the TIBP and LWP breeds, including MYF5, MYOF, ASB2, PDE9A, SDC1, PDGFRA, MYOM2, ACVR1, ZIC3, COL11A1, TGFBR1, EDNRA, TGFB2, PDE4D, PGAM2, GRK2, SCN4B, CACNA1S, MYL4, IGF1, and FOXO1. Additionally, genes such as CAPN3, MYOM2, and PGAM2, identified as both DEPs and DEGs related to skeletal muscle development, contained multiple TIBP-specific and LWP-predominant SNPs in regulatory and/or coding regions, underscoring significant ΔAF differences between the two breeds.Conclusion: This comprehensive investigation of SNPs in DEGs and DEPs identified a significant number of SNPs and genes related to skeletal muscle development during the prenatal stage. These findings not only shed light on potential causal genes for muscle divergence between the TIBP and LWP breeds but also offer valuable insights for pig breeding strategies aimed at enhancing meat production.

2024-11-01·Microcirculation

PDE9A Inhibition Improves Coronary Microvascular Rarefaction and Left Ventricular Diastolic Dysfunction in the ZSF1 Rat Model of HFpEF

Article

作者: Lang, Liwei ; Buncha, Vadym ; Bagi, Zsolt ; Fopiano, Katie Anne ; Pearson, William M. ; Zhazykbayeva, Saltanat ; El‐Battrawy, Ibrahim ; Hamdani, Nazha ; Hardell, Davis J.

ABSTRACTObjectiveHeart failure with preserved ejection fraction (HFpEF) commonly arises from comorbid diseases, such as hypertension, obesity, and diabetes mellitus. Selective inhibition of phosphodiesterase 9A (PDE9A) has emerged as a potential therapeutic approach for treating cardiometabolic diseases. Coronary microvascular disease (CMD) is one of the key mechanisms contributing to the development of left ventricular (LV) diastolic dysfunction in HFpEF. Our study aimed to investigate the mechanisms by which PDE9A inhibition could ameliorate CMD and improve LV diastolic function in HFpEF.Methods and ResultsThe obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model of HFpEF was employed in which it was found that a progressively developing coronary microvascular rarefaction is associated with LV diastolic dysfunction when compared to lean, nondiabetic hypertensive controls. Obese ZSF1 rats had an increased cardiac expression of PDE9A. Treatment of obese ZSF1 rats with the selective PDE9A inhibitor, PF04447943 (3 mg/kg/day, oral gavage for 2 weeks), improved coronary microvascular rarefaction and LV diastolic dysfunction, which was accompanied by reduced levels of oxidative and nitrosative stress markers, hydrogen peroxide, and 3‐nitrotyrosine. Liquid chromatography–mass spectrometry (LC–MS) proteomic analysis identified peroxiredoxins (PRDX) as downregulated antioxidants in the heart of obese ZSF1 rats, whereas Western immunoblots showed that the protein level of PRDX5 was significantly increased by the PF04447943 treatment.ConclusionsThus, in the ZSF1 rat model of human HFpEF, PDE9A inhibition improves coronary vascular rarefaction and LV diastolic dysfunction, demonstrating the usefulness of PDE9A inhibitors in ameliorating CMD and LV diastolic dysfunction through augmenting PRDX‐dependent antioxidant mechanisms.

2024-08-01·Journal of Cardiovascular Translational Research

Exploration of the Potential Biomarker FNDC5 for Discriminating Heart Failure in Patients with Coronary Atherosclerosis

Article

作者: Zheng, Yuntao ; Liu, Siyu ; Jiang, Lingling ; Zheng, Hongchao ; Huang, Wei ; Cao, Richard Y ; Miao, Peizhi ; Zhu, Ning

Coronary atherosclerosis leading to ischemic artery disease is one of the etiological factors to develop heart failure (HF). This study aimed to investigate potential biomarkers for discriminating HF in atherosclerotic patients. This study included 40 consecutive atherosclerotic patients who underwent angiography. Concentrations of B-type natriuretic peptide (BNP), fibronectin type III domain containing 5 (FNDC5), and Phosphodiesterase 9A (PDE9A) were measured in 20 atherosclerotic patients with HF symptoms/signs and 20 without HF symptoms/signs. Circulating BNP levels were elevated, while FNDC5 levels were reduced in atherosclerotic patients with HF symptoms/signs compared to those without HF symptoms/signs. Pearson correlation analysis showed a significant correlation between FNDC5 and BNP. Receiver Operating Characteristics analysis indicated that both FNDC5 and BNP were able to discriminate HF in atherosclerotic patients. Our findings suggest that FNDC5, along with BNP, has independent value as a biomarker for discriminating HF in patients with coronary atherosclerosis.

项与 PDE9A 相关的新闻（医药）

2025-03-03

·医药观澜

8家创新药公司完成新一轮融资！1家来自中国

▎药明康德内容团队报道根据公开信息，上周（2月24日~3月2日），全球范围内有至少8家致力于创新药研发的新锐公司宣布完成新一轮融资，其中1家来自中国。通过梳理，这些获得资本青睐的新锐公司正在开发的产品包括小分子、抗体、细胞和基因疗法等，针对的疾病涵盖了癌症、神经系统疾病、自身免疫性疾病，以及蛋白质错误折叠相关疾病等。抟相医药融资轮次：Pre-A轮融资金额：数千万元 2月24日，抟相医药宣布完成数千万人民币Pre-A轮融资。本轮融资由浦东创投集团旗下浦东科技投资天使母基金领投，老股东比邻星创投继续追加投资。此轮融资用于推进管线的研发以及加速“液-液相分离”技术平台开发，包括推进自免及肿瘤管线IND申报。抟相医药成立于2022年，是一家兼具传统新药研发和利用独特相分离技术的创新药研发公司。该公司目前正在推进解决包含自免疾病、中枢神经系统疾病、肿瘤等疾病领域难成药靶点的开发痛点。 Inceptor Bio 融资轮次：A2轮融资金额：2100万美元 2月25日，Inceptor Bio宣布完成2100万美元的A2轮系列融资。Inceptor Bio致力于推进治疗癌症的下一代细胞和基因疗法。该公司同时宣布，其先导项目IB-T101治疗透明细胞肾细胞癌（ccRCC）的IIT临床试验完成首例患者给药。IB-T101是一种自体CD70 CAR-T疗法，该产品的开发基于Inceptor Bio的新型平台OUTLAST，该平台对T细胞进行代谢重编程，使其在恶劣的肿瘤微环境（TME）中茁壮成长。本轮融资将支持IB-T101的持续临床开发和下一代细胞治疗管道的扩展。 Paradox 融资轮次：未披露融资金额：1000万美元 2月25日，Paradox Immunotherapeutics宣布获得SymBiosis领投的1000万美元融资，用于推进蛋白质错误折叠疾病的治疗。Paradox专注于开发治疗蛋白质错误折叠疾病的创新抗体疗法，其设计并开发了专门的抗体，可以选择性地靶向并清除有问题或错误折叠的蛋白质，同时使健康蛋白质不受影响。该公司目前正专注于开发免疫球蛋白轻链淀粉样变性（AL淀粉样变性）的治疗方法，AL淀粉样变性是多发性骨髓瘤的一种并发症，可导致心脏、肾脏和肝脏衰竭；以及推进白细胞趋化因子2淀粉样变性（LECT2）的治疗方法，LECT2往往会导致慢性肾脏疾病和衰竭。 Monument 融资轮次：种子轮融资金额：85万英镑 2月25日，Monument Therapeutics宣布获得了由ACF Investors领投的85万英镑种子轮融资。Monument是一家创新的神经科学公司，致力于将数字生物标志物应用于精神药物开发。该公司目前正在1期临床研究中探索开发MT1988，这是一种治疗与精神分裂症相关的认知障碍（CIAS）的新型固定剂量联合药物，其通过结合两种特性良好的作用于尼古丁受体的小分子，旨在增强CIAS患者认知功能，同时减轻类似治疗常见的副作用。该药物旨在与现有的抗精神病药物一起使用，为患者提供补充解决方案。 Fuse Vectors 融资轮次：Pre-种子轮融资金额：520万美元 2月26日，Fuse Vectors宣布获得HCVC领投的520万美元Pre-种子轮融资。该公司致力于以无细胞（cell-free）病毒载体技术革新基因治疗的发展进程。Fuse Vectors的技术旨在改变基因疗法依赖活细胞的传统模式，通过受控的生化反应组装病毒载体显著提高精度和效率，并将基因治疗的可及性扩展到更广泛的适应症。本次融资资金将用于加速该公司技术平台和新型基因治疗管线的开发，以满足更广泛的患者需求。 Ignota Labs 融资轮次：种子轮融资金额：690万美元 2月26日，Ignota Labs宣布完成690万美元（550万英镑）的种子轮融资，由Montage Ventures和AIX Ventures共同领投。根据新闻稿介绍，药物安全性是新药临床试验失败的主要原因之一，这使得大部分在研新药无法最终到达患者手中。Ignota Labs致力于通过应用深度学习、化学信息学和生物信息学来解决这个问题，以发现和解决药物毒性的根本原因，为因安全性原因可能被放弃的资产释放新的机会。本轮融资资金将用于通过收购更多的“不良资产”扩大在研管线，并推进该公司首个产品PDE9A抑制剂的早期临床试验。 Eikon Therapeutics 融资轮次：D轮融资金额：3.507亿美元 2月26日，Eikon Therapeutics宣布完成3.507亿美元D轮融资。该公司正通过科学与工程的深度融合推进突破性疗法的研发。公司独有的技术平台结合曾获得诺贝尔化学奖的超分辨率显微技术、先进工程学和高性能计算，实现了对活细胞中蛋白质实时运动的精准可视化与定量测量，旨在为患有重大疾病的患者带来全新的治疗选择。Eikon的临床阶段管线包括Toll样受体7和8的共激动剂EIK1001，正处于治疗晚期黑色素瘤的3期试验阶段；高选择性的PARP1抑制剂EIK1003，目前正于乳腺癌、卵巢癌、前列腺癌或胰腺癌患者中开展1期试验；一种可进入中枢神经系统的PARP1选择性抑制剂EIK1004，预计启动针对脑癌的1期研究。 Enveda Biosciences 融资轮次：C轮融资金额：1.5亿美元 2月27日，Enveda宣布获得赛诺菲（Sanofi）的投资，用于推进人工智能驱动的药物研发到临床试验阶段，这使得该公司C轮融资总额达到1.5亿美元。Enveda是一家生物技术公司，其致力于从生命的化学中学习，以更快地创造更好的药物。Enveda使用人工智能驱动的工具来识别和表征生物产生的各种分子——其中绝大多数从未被科学探索过。该公司目前正在推进一种口服小分子药物ENV-294用于治疗特应性皮炎和哮喘。本轮融资还将推动该公司在2025年进一步扩大临床产品管线，并增强其人工智能驱动的发现能力。期待在资本的助力下，更多前沿疗法和技术能够更快惠及患者。参考资料： [1]各公司官网及公开资料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。转载授权或其他合作需求，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。

临床1期细胞疗法临床申请免疫疗法基因疗法

2025-02-26

·Endpoints

Harbour BioMed inks deal up to $395M; ORIC refines plans for two drugs

Plus, news about Idorsia, Enveda, Zymeworks, BerGenBio and Ignota Labs: Harbour BioMed does another deal: The Shanghai-based biotech’s subsidiary, called HBM Alpha Therapeutics, inked a pact with an undisclosed company for up to $395 million in upfront fees and biobucks, plus the potential for a minority stake. The undisclosed partner also gets exclusive ex-China global rights to an antibody known as HAT001/HBM9013 for congenital adrenal hyperplasia (CAH) and other rare endocrine disorders. HBMAT raised a seed round of undisclosed size in January 2023, and Harbour did a NewCo deal for an anti-TSLP antibody with Windward Bio last month. — Kyle LaHucik ORIC ‘refines’ development plans for two drugs: The ORIC-944 program is set to start a Phase 3 trial in the first half of 2026 looking at patients with metastatic castration-resistant prostate cancer. Its ORIC-114 candidate is expected to begin registrational trials sometime in 2026 in the first-line lung cancer setting. Its stock $ORIC was up about 13% on Wednesday morning. — Max Gelman Idorsia’s big updates: The Swiss drugmaker said an undisclosed party opted not to move forward with a deal for the global rights to Idorsia’s experimental hypertension drug, called aprocitentan, but it will keep the $35 million exclusivity fee that it got in December. Meanwhile, Idorsia and Viatris adjusted the terms of their collaboration for selatogrel and cenerimod, with Idorsia contributing $100 million less toward development while losing $250 million in potential milestone payments from Viatris. It is also restructuring its debt and getting new funding . — Kyle LaHucik Sanofi backs Enveda with $20M: The French pharma giant is joining the Series C of the Colorado biotech, which mines plant chemistry to find new drugs. The Series C now totals $150 million, up from the $130 million disclosed in November . — Kyle LaHucik Zymeworks’ $14M milestone: The company received the payment from GSK from a bispecific antibody deal they inked in 2016 and then expanded in 2019. — Jaimy Lee BerGenBio discontinues lung cancer study, to seek strategic alternatives: The company was evaluating whether bemcentinib, an AXL kinase inhibitor, could treat patients with first-line non-squamous non-small cell lung cancer in combination with standard of care. Patients also needed to have a mutation of the STK11 gene. In a statement, CEO Olav Hellebø said the results were not strong enough for BerGenBio to obtain additional financing and is now looking for a merger, sale or other transaction. — Max Gelman Ignota Labs closes £5.5M seed round: The startup’s goal is to “turn around failed drugs” using AI, acquiring assets from bigger companies that stopped being developed and then testing them in new clinical trials. Its first asset is a PDE9A inhibitor, which the company says has potential in cardiovascular, metabolic and neurodegenerative diseases. — Max Gelman

引进/卖出抗体药物偶联物

2023-02-20

·医药观澜

速递！药捷安康获2.6亿元D+轮融资

2月20日，药捷安康宣布完成2.6亿元人民币D+轮融资。本轮融资由国鑫投资领投，三一创新投资、国联金投启源、南京江北国资、中银资本、百益德投资、瑞桐创投、敦行资本跟投。药捷安康是一家处于临床阶段的生物制药公司，专注于发现和开发肿瘤、炎症及心血管疾病领域的小分子创新疗法，解决临床难治性疾病。目前，药捷安康共有7款在研产品处于不同的临床研发阶段。其中，药捷安康的核心产品tinengotinib（TT-00420）是一款创新的激酶谱选择性抑制剂，通过靶向肿瘤细胞和改善肿瘤微环境发挥抗肿瘤作用，有望解决FGFR抑制剂耐药等多个临床问题。目前，该产品正在中国和美国开展多项2期临床研究，正在开发的适应症还包括三阴乳腺癌、胆道系统癌症、转移性去势抵抗性前列腺癌等。该产品还曾获得美国FDA授予针对胆管癌的孤儿药资格和快速通道资格。根据药捷安康公开资料，该公司的在研产品还包括：1）TT-00973，一款新型AXL/FLT双靶点抑制剂；2）TT-01688，药捷安康从LG chem公司引进的一款全新的SIPI受体小分子调节剂；3）TT-01488，一款非共价可逆BTK抑制剂；4）TT-00434，一种新型的、高活性和高选择性FGFR1/2/3抑制剂；5）TT-00920，一款高选择性PDE9抑制剂；6）TT-01025，药捷安康从LG chem公司引进的一种新型的氨基脲敏感性胺氧化酶/血管黏附蛋白1（SSAO/VAP-1）抑制等等。这些产品正在开发的适应症包括多种实体瘤、血液系统恶性肿瘤、特应性皮炎、心力衰竭等。药捷安康创始人、董事长吴永谦博士表示，本轮融资的顺利完成，标志着各方投资者对药捷安康创新理念和价值创造的认可。它们将继续加速公司国际化、商业化的进程，守正创新，打造有国际影响力的生物技术公司。参考资料：[1]药捷安康宣布完成D+轮融资. Retrieved Feb 20 , 2023. From https://mp.weixin.qq.com/s/SxcTjsH0z0ouImgIKq9vbQ[2]药捷安康官网. From http://www.transtherabio.com/En/Index/index 内容来源于网络，如有侵权，请联系删除。

快速通道孤儿药