主要目的：确定HRS8807单药及联合SHR6390在晚期乳腺癌患者中的DLT，MTD和RP2D；同时评价研究药物安全性。次要目的：评估单次/多次给药后药代动力学（PK）参数；联合SHR6390阶段单次/多次给药后药代动力学（PK）参数；初步评价HRS8807及联合SHR6390疗效；评价HRS8807多次给药对咪达唑仑药代动力学的影响。

开始日期2021-10-26

申办/合作机构

上海恒瑞医药有限公司

[+1]

NCT04993430 / Recruiting临床1期

A Phase 1, Single Arm, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability and Pharmacokinetic of HRS8807 Monotherapy and in Combination With SHR6390 in Subjects With ER-Positive, HER2-Negative Metastatic or Locally Advanced Breast Cancer

The study is to assess safety and tolerability of HRS8807 monotherapy and in combination with SHR6390 in subjects with metastatic or locally advanced breast cancer in order to estimate the Dose-Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D).

开始日期2021-10-26

申办/合作机构

上海恒瑞医药有限公司

NCT02876003 / Withdrawn临床2期

An Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy, Safety and CNS Exposure of G-202 in Patients With PSMA Positive Recurrent or Progressive Glioblastoma

Glioblastoma (GBM) comprises about 16% of all malignancies of the nervous system and over 50% of all gliomas. Standard of care for newly-diagnosed GBM is a combination of surgical debulking followed by concurrent radiotherapy and chemotherapy with temozolomide. Efforts to improve second-line therapy in GBM have met with only marginal success and there is a large unmet medical need for new therapies. G-202 (mipsagargin) is an example of prodrug chemotherapy. It is activated by Prostate Specific Membrane Antigen (PSMA), which is expressed by some cancer cells and in the blood vessels of most solid tumors, including GBM, but not by normal cells or blood vessels in normal tissue. It is believed that activation of the prodrug G-202 will allow the drug to kill cancer cells. This study will evaluate the activity, safety and CNS exposure of G-202 in patients with PSMA-positive recurrent or progressive GMB receiving G-202 by intravenous infusion on three consecutive days of a 28-day cycle.

开始日期2016-09-01

申办/合作机构

Rebus Holdings, Inc.

100 项与 SERCA 相关的临床结果

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100 项与 SERCA 相关的转化医学

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0 项与 SERCA 相关的专利（医药）

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项与 SERCA 相关的文献（医药）

2025-01-01·Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology

O-GlcNAcylation of SERCA protects skeletal muscle in hibernating Spermophilus dauricus from disuse atrophy

Article

作者: Cao, Mengru ; Dang, Kai ; Kong, Yong ; Wang, Huiping ; Yang, Huajian ; Qian, Airong ; Gao, Yuan

Long-term inactivity of skeletal muscle results in muscular disuse atrophy; however, hibernating animals do not experience muscular disuse atrophy during the hibernation period. The molecular mechanism underlining the anti-atrophy effect in these animals is unclear. O-linked N acetyl-β-D-glucosaminylation (O-GlcNAcylation) and its effect on cell signaling pathways are important mechanisms underlying muscular disuse atrophy; thus, in this study, we investigated O-GlcNAcylation changes during hibernation in Spermophilus dauricus to explore the role of O-GlcNAcylation in the muscle disuse atrophy resistance of hibernating animals. The results showed that during hibernation, the muscle fiber cross-sectional area and ratio of muscle fiber did not change, and the morphological structure of the muscle remained intact, with normal contractile function. The level of O-GlcNAcylation decreased during hibernation, but quickly returned to normal in the periodic arousal stage. The O-GlcNAcylation level of sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) decreased, whereas its activity increased. The decrease in O-GlcNAcylation of SERCA could result in the decreased binding of phospholamban to SERCA1, thus decreasing its inhibition to SERCA1 activity. This in turn can inhibit muscle cell calcium overload, maintain muscle cell calcium homeostasis, and stabilize the calpain proteolytic pathway, ultimately inhibiting skeletal muscle atrophy. Our results demonstrate that periodic arousal along with returning O-GlcNAcylation level to normal are important mechanisms in preventing disuse atrophy of skeletal muscle during hibernation.

2024-11-01·Biochemical and Biophysical Research Communications

SERCA pump as a novel therapeutic target for treating neurodegenerative disorders

Review

作者: Bezprozvanny, Ilya ; Dahl, Russell

The neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Spinocerebellar ataxias (SCAs), present an enormous medical, social, financial and scientific problem. Despite intense research into the causes of these disorders, only marginal progress has been made in the clinic and no cures exist for any of them. Most of the scientific effort has been focused on identification of the major causes of these diseases and on developing ways to target them, such as targeting amyloid accumulation for AD or targeting expression of mutant Huntingtin for HD. Calcium (Ca²⁺) signaling has long been proposed to play an important role in the pathogenesis of neurodegenerative disorders, but blockers of Ca²⁺ channels and Ca²⁺ signaling proteins have not been translated to clinic primarily due to side effects related to the important roles of target molecules for these compounds at the peripheral tissues. In this review article, we would like to discuss an idea that recently identified positive allosteric modulators (PAMs) of the sarco-endoplasmic reticulum calcium (SERCA) pump may provide a promising approach to develop therapeutic compounds for treatment of these disorders. This hypothesis is supported by the preclinical data obtained with animal models of AD and PD. The first critical test of this idea will be an imminent phase I study that will offer an opportunity to evaluate potential side effects of this class of compounds in humans.

2024-11-01·American Journal of Physiology-Heart and Circulatory Physiology

Cellular calcium handling and electrophysiology are modulated by chronic physiological pacing in human induced pluripotent stem cell-derived cardiomyocytes

Article

作者: Fink, Sarah ; Nahrendorf, Matthias ; Reetz, Florian ; Knierim, Maria ; Voigt, Niels ; Pöppl, Arnold ; Riedl, Dominic ; Paulus, Michael ; Streckfuss-Bömeke, Katrin ; Bommer, Thea ; Sossalla, Samuel ; Pabel, Steffen ; Wang, Peter ; Maier, Lars S

Electric pacing is increasingly used in research with human induced pluripotent stem cell cardiomyocytes (hiPSC-CM), for example to simulate arrhythmias but also to enhance maturity. Therefore, it is mandatory to understand the effects of pacing itself on cellular electrophysiology in late-stage, matured hiPSC-CM. This study provides an electrophysiological characterization of the effects of chronic electric pacing at a physiological rate on differentiated hiPSC-CM.

项与 SERCA 相关的新闻（医药）

2024-10-23

·医药观澜

正大天晴两款乳腺癌1类新药获批临床

▎药明康德内容团队报道 10月22日，中国国家药监局药品审评中心（CDE）官网公示，正大天晴两款1类新药获得临床试验默示许可，适应症为TQB3616胶囊联合TQB3912片和氟维司群注射液，用于治疗晚期HR阳性、HER2阴性乳腺癌。公开资料显示，TQB3616（库莫西利胶囊，culmerciclib）是一种CDK2/4/6抑制剂，TQB3912是一种AKT抑制剂。截图来源：CDE官网乳腺癌是中国女性最常见的恶性肿瘤。近年来，乳腺癌发病率和死亡率均呈上升趋势，其中，约60%~70%的乳腺癌患者为HR阳性、HER2阴性。公开资料显示，尽管大多数HR+/HER2-乳腺癌患者初始可从内分泌和CDK4/6抑制剂或者化疗中获益，但一段时间后，大部分可能会产生耐药，导致治疗失败。库莫西利是正大天晴在研的一款周期蛋白依赖性激酶2、4和6（CDK2/4/6）抑制剂，对CDK2、CDK4、CDK6激酶有不同程度的抑制效果。研究结果显示，其增强的CDK2和CDK4抑制活性可能有助于在临床上克服目前CDK4/6抑制剂的耐药性问题。今年7月，CDE已经受理库莫西利联合氟维司群用于既往内分泌经治的HR阳性、HER2阴性局部晚期或转移性乳腺癌适应症的上市申请。今年9月，正大天晴公布了库莫西利胶囊联合氟维司群在针对内分泌经治的HR+/HER2-晚期乳腺癌3期临床（TQB3616-III-01）的最新成果，中位无进展生存期（PFS）为16.62个月，较对照组PFS延长9.16个月；库莫西利联合治疗将疾病进展/死亡风险降低64%；客观缓解率（ORR）为40.21%，总生存期（OS）呈获益趋势。 TQB3912则是一种AKT抑制剂，该产品目前正在针对晚期恶性肿瘤受试者开展1期临床研究。AKT是一种丝氨酸/苏氨酸激酶，处于PI3K/AKT信号通路的下游。AKT通路的过度激活是驱动癌症生长的关键途径之一，在复发性卵巢癌、乳腺癌和前列腺癌等肿瘤中尤为普遍，而且AKT的激活与对激素疗法产生的抗性相关。AKT也由此成为了治疗肿瘤的热门靶点。本次AKT抑制剂联合CDK2/4/6抑制剂获批临床，意味着正大天晴将开展新的联合疗法治疗乳腺癌的临床研究。根据正大天晴公开资料，在乳腺癌领域，该公司布局了丰富的创新产品管线，包括CDK2/4/6抑制剂库莫西利，还有TQB2102（HER2双抗ADC）、TQB2930（HER2双抗）、TQB3912（AKT抑制剂）、TQB3915（SERCA拮抗剂）、PARP1抑制剂、ER靶向降解剂等创新药。参考资料： [1] 中国国家药监局药品审评中心官网. Retrieved Oct 22, 2024, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c [2]乳腺癌1类新药库莫西利III期研究入选全国临床肿瘤学大会口头报告. Retrieved Aug 30, 2024, from https://mp.weixin.qq.com/s/NDQSM9E_rI7tDrx0fpbgPw [3]主要终点PFS双重显著获益！正大天晴乳腺癌1类新药库莫西利亮相2024 CSCO. Retrieved Sep 27, 2024, from https://mp.weixin.qq.com/s/rYtVR4WL_l-8vCYZtUyICw 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。转载授权及其他合作需求，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3期申请上市抗体药物偶联物临床1期临床2期

2024-08-29

·正大天晴药业集团

乳腺癌1类新药库莫西利III期研究入选全国临床肿瘤学大会口头报告

9月25日至29日，第27届中国临床肿瘤学大会暨2024年CSCO学术年会将在厦门召开。正大天晴将在创新专场以口头报告形式公布1类创新药库莫西利胶囊（TQB3616）联合氟维司群治疗内分泌经治的激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）晚期乳腺癌的III期研究最新成果。今年7月，该联合疗法上市申请已获国家药监局药品审评中心受理，有望成为公司在乳腺癌领域首个创新药。库莫西利是一种新型周期蛋白依赖性激酶2、4和6（CDK2/4/6）抑制剂，对CDK2、CDK4、CDK6激酶有不同程度的抑制效果，并且对CDK4激酶具有较强的抑制能力[1]。研究结果显示，库莫西利对CDK2具有抑制作用，其增强的CDK2和CDK4抑制活性可能有助于在临床上克服目前CDK4/6抑制剂的耐药性问题[1]。摘要标题：TQB3616联合氟维司群治疗激素受体阳性、HER2阴性晚期乳腺癌：一项随机、双盲、平行对照的3期临床试验入选形式：创新专场口头报告通讯作者：中国人民解放军总医院第五医学中心江泽飞第一作者：江苏省人民医院殷咏梅这是一项随机、双盲、平行对照、多中心III期临床研究，旨在评估库莫西利联合氟维司群和对照组在既往内分泌经治的HR阳性、HER2阴性晚期乳腺癌的有效性和安全性。研究显示，相较于对照组，库莫西利联合氟维司群可显著降低HR+/HER2-晚期乳腺癌患者的疾病进展或死亡风险，同时改善客观缓解率（ORR）、CBR（临床获益率）、OS（总生存期）等次要终点。详细研究数据将于本次大会披露。乳腺癌是中国女性最常见的十大恶性肿瘤中发病率排在第二位的癌症，中国每年新发病例数达36万[2]。近年来，乳腺癌发病率和死亡率均呈上升趋势，其中，约60%-70%的乳腺癌患者为HR阳性、HER2阴性。在乳腺癌领域，公司布局了丰富的创新产品管线，除了库莫西利，还有TQB2102（HER2双抗ADC）、TQB2930（HER2双抗）、TQB3912（AKT抑制剂）、TQB3915（SERCA拮抗剂）、PARP1抑制剂、ER PROTAC降解剂等创新药。本次CSCO年会，正大天晴还将公布其他20多项最新研究成果，全面展示在多个肿瘤治疗领域取得的突破性进展。未来，公司将继续聚焦肿瘤领域创新，深入探索创新药物与治疗方案，以期为肿瘤患者带来更多获益，让健康科技，温暖更多生命。资料来源： [1] Xu Z, Liu Y, Song B, et al. Discovery and preclinical evaluations of TQB3616, a novel CDK4-biased inhibitor. Bioorganic & Medicinal Chemistry Letters 2024; 107. [2] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 2024; 74(3): 229-63. 声明： 1. 本新闻稿旨在促进医药信息的沟通和交流，仅供医疗卫生专业人士参阅，非广告用途。 2. 本公司不对任何药品和/或适应症作推荐。 3. 本新闻稿中涉及的信息仅供参考，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。若您想了解具体疾病诊疗信息，请遵从医生或其他医疗卫生专业人士的意见或指导。 ›› 创新药引领增长中国生物制药上半年营收利润皆实现双位数增长半年营收158.7亿创新高 ›› 荣誉再+1！正大天晴明星产品入选2024健康产业品牌榜 ›› 携手推动数字化转型正大天晴与华为签署全面合作协议

抗体药物偶联物CSCO会议临床3期临床1期蛋白降解靶向嵌合体

2024-07-19

·正大天晴药业集团

正大天晴乳腺癌领域1类新药库莫西利上市申请获受理

7月18日，正大天晴自主研发的1类创新药库莫西利胶囊（Culmerciclib，TQB3616）联合氟维司群注射液（商标名：晴可依），已向国家药监局药品审评中心（CDE）递交新药上市申请并获受理，用于既往内分泌经治的激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性局部晚期或转移性乳腺癌的治疗。乳腺癌是女性最常见的恶性肿瘤之一，库莫西利有望成为公司在该领域的首个创新药。在这一领域，公司还布局有HER2双抗的ADC药物TQB2102、HER2双抗药物TQB2930、AKT、SERCA、PARP1、ER PROTAC等创新药。库莫西利是一种新型周期蛋白依赖性激酶2、4和6（CDK2/4/6）抑制剂，对CDK2、CDK4、CDK6激酶有不同程度的抑制效果，并且对CDK4激酶具有较强的抑制能力[1]。研究结果显示，库莫西利对CDK2具有抑制作用，其增强的CDK2和CDK4抑制活性可能有助于在临床上克服目前CDK4/6抑制剂的耐药性问题[1]。乳腺癌是中国女性最常见的十大恶性肿瘤中发病率排在第二位的癌症，中国每年新发病例数达36万[2]。近年来，乳腺癌发病率和死亡率均呈上升趋势，其中，约60%-70%的乳腺癌患者为HR阳性、HER2阴性。公司在乳腺癌领域的创新药研发上不断取得突破。此次获受理的库莫西利作为一款新型CDK2/4/6抑制剂，将为HR+/HER2-乳腺癌患者提供新的治疗选择；HER2双抗的ADC药物TQB2102也将近期启动关键注册临床试验。随着多项在研创新项目陆续进入收获期，公司有望为更多女性患者提供更加丰富的治疗选择。除上述创新药外，公司在乳腺癌治疗领域还开发了多种仿制药与生物类似药。氟维司群注射液（商标名：晴可依）、依维莫司片（商标名：晴维时）、注射用曲妥珠单抗（商标名：赛妥）等重磅产品已经上市，其中，氟维司群于2020年8月获批上市，为国内首仿，且出口欧美。另外，帕妥珠单抗注射液正在CDE上市技术审评中。这些作为HR+、HER2+乳腺癌治疗药品，可减轻患者的用药负担，大大提高药物可及性。参考文献： 1. Xu Z, Liu Y, Song B, et al. Discovery and preclinical evaluations of TQB3616, a novel CDK4-biased inhibitor. Bioorganic & Medicinal Chemistry Letters 2024; 107. 2. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 2024; 74(3): 229-63. 声明： 1. 本新闻稿旨在促进医药信息的沟通和交流，仅供医疗卫生专业人士参阅，非广告用途。 2. 本公司不对任何药品和/或适应症作推荐。 3. 本新闻稿中涉及的信息仅供参考，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。若您想了解具体疾病诊疗信息，请遵从医生或其他医疗卫生专业人士的意见或指导。 ›› 谢承润应邀出席福布斯中国U30十周年峰会勉励年轻人自我修炼、坚定成长 ›› 彰显创新实力！正大天晴连续9年荣登中国药品研发综合实力百强榜前3强 ›› Ⅰ类创新药三连发！正大天晴新一代ALK抑制剂依奉阿克获批上市

抗体药物偶联物上市批准蛋白降解靶向嵌合体