Advanced cervical cancer patients treated with standard of care (SOC) chemoradiation plus glutaminase inhibition with telaglenastat (CB-839) will have increased progression-free survival (PFS) compared to historical rates for patients receiving SOC chemoradiation alone.

开始日期2025-05-31

申办/合作机构

Washington University School of Medicine

[+2]

NCT05039801

/ Recruiting临床1期IIT

A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid Tumors

To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.

开始日期2021-09-09

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT04824937

/ Unknown status临床2期IIT

A Phase II Study of the Glutaminase Inhibitor Telaglenastat (CB-839) in Combination With the PARP Inhibitor Talazoparib in Participants With Metastatic Castration-Resistant Prostate Cancer

The purpose of this research is to test the effectiveness of an experimental drug combination for people with metastatic castration-resistant prostate cancer (mCRPC).
The names of the study drugs involved in this study are:
Telaglenastat (CB-839)
Talazoparib

开始日期2021-07-01

申办/合作机构

The General Hospital Corp.

[+3]

100 项与 GLS 相关的临床结果

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100 项与 GLS 相关的转化医学

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0 项与 GLS 相关的专利（医药）

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项与 GLS 相关的文献（医药）

2025-08-01·Food Chemistry

Pickering emulsion stabilized by protein-glutaminase modified soybean isolated proteins as a new delivery system

Article

作者: Ding, Yunan ; Liu, Yihan ; Li, Ziyuan ; Hou, Jiayi ; Wang, Kangning ; Lu, Fuping ; Jia, Yiyang

Plant protein-based Pickering emulsions have garnered significant attention for their natural, stable, and efficient properties. However, the aggregation and sedimentation of plant proteins have restricted their applications in the food industry. To address this challenge, the current study explored the effect of protein-glutaminase on the structural characteristics of soy protein isolate (SPI) and assessed the potential of emulsions prepared from deamidated SPI as carriers for bioactive compounds. Structural characterization of SPI at varying degrees of deamidation (DD) revealed that deamidation notably enhanced the solubility, emulsifying ability, and surface charge density of SPI, while preserving its higher-order structure. Moreover, SPI Pickering emulsions with moderate deamidation (5 % DD) demonstrated increased droplet density, a more compact microstructure, improved rheological properties, and enhanced light stability. Additionally, in vitro digestion studies showed that deamidated SPI Pickering emulsions could effectively deliver bioactive compounds. This study offers new insights into developing legume protein-based Pickering emulsions with superior performance.

2025-08-01·Toxicology

Embryonic exposure to GenX causes reproductive toxicity by disrupting the formation of the blood-testis barrier in mouse offspring

Article

作者: Li, Shuhao ; Pan, Chun ; Ma, Tan ; Chen, Hao ; Kong, Liang ; Hong, Runyang ; Zhou, Qiyue ; Fan, Zhencheng

As a replacement for perfluorooctanoic acid, hexafluoropropylene oxide dimer acid, commercially referred to as "GenX", has attracted significant attention. However, a comprehensive understanding of the reproductive systems of male offspring exposed to GenX is lacking. This study aimed to investigate how embryonic exposure to GenX affects the reproductive development of male offspring and the underlying mechanisms. We administered GenX daily via gavage (2 mg/kg body weight/day) to the mice from day 12.5 of pregnancy until delivery. Our results suggested that embryonic exposure to GenX led to delayed onset of puberty in male offspring, with destruction of the testicular structure, disruption of the blood-testis barrier, decreased serum testosterone levels, decreased sperm count, impaired sperm motility, and increased rates of sperm abnormalities. We investigated the mechanism of blood-testis barrier breakdown in vitro by treating Sertoli cells (TM4) with GenX. GenX exposure caused the accumulation of senescent TM4 cells, decreased their glutathione (GSH) levels, and increased their oxidized glutathione levels. GenX inhibited glutaminase activity in TM4 cells, leading to decreased GSH synthesis, increased intracellular oxidative stress, and subsequent TM4 cell senescence, ultimately compromising the blood-testis barrier. Our findings indicated that embryonic exposure to GenX may cause Sertoli cell senescence by altering glutamine metabolism, disrupting the blood-testis barrier, and resulting in abnormal reproductive development in male offspring.

2025-07-01·Food Chemistry

Gelation potential of oat protein isolate: Influence of extraction method, gelling conditions, and enzymatic modification

Article

作者: Laitinen, Miikka ; Maina, Ndegwa H ; Jouppila, Kirsi ; Kokkonen, Tiina ; Huang, Xin ; Mäkelä-Salmi, Noora

The poor technological functionality of oat protein presents a challenge in food applications. This study investigated the effect of extraction method, gelling conditions (pH and NaCl concentration), and enzymatic modification on heat-induced gelation of oat protein isolate (OPI). Fairly strong gels (G' = 5000 Pa, tan δ = 0.26) were formed from OPI, but gelation was highly sensitive to pH and NaCl concentration. Extraction at pH ∼10 negatively affected the gelation properties compared to extraction at pH 8. Partial hydrolysis with alcalase, bromelain, or papain increased the solubility of OPI but was detrimental to gelation, leading to liquid expulsion from the gel. After enzymatic deamidation with protein glutaminase, up to 87 % solubility of OPI at pH 7 was achieved, and it formed soft, elastic, and slightly translucent gels (G' = 1100 Pa, tan δ = 0.21). The extraction process and modifications of oat proteins have a great impact on their techno-functionality and need optimization for food applications.

项与 GLS 相关的新闻（医药）

2025-05-01

·PRNewswire

Synhale Therapeutics Acquires Telaglenastat, Accelerates Development for Pulmonary Hypertension Treatment

PITTSBURGH and BOSTON, May 1, 2025 /PRNewswire/ -- Synhale Therapeutics Inc. (Synhale), a virtual, clinical-stage biotech company committed to transforming Pulmonary Hypertension (PH), announced the acquisition of Telaglenastat (CB-839), the first-in-class glutaminase inhibitor. Synhale is advancing into a Phase 2 clinical program across PH Groups 1-4. "This acquisition represents a unique opportunity to rapidly deliver clinical data addressing a disease with high mortality and substantial market potential," said Chad D. Holland, President & CEO of Synhale. "Leveraging Telaglenastat's prior human clinical experience, our capital-efficient model aims to accelerate transformative therapy to patients while maximizing shareholder value." Stephen Chan, MD, PhD, Founder of Synhale, added, "The unmet patient need in PH is immense, particularly in Groups 2 and 3, where heart failure with preserved ejection fraction (HFpEF) and chronic lung disease remain deadly and underserved. PH with HFpEF carriers a five-year mortality approaching 50%, with similarly grim outcomes in COPD and other lung diseases. By targeting glutaminase activity, we address a fundamental metabolic pathway across all PH groups, offering hope to patients with few options." PH, a severe condition, is characterized by remodeling and stiffening in the pulmonary vasculature and often dramatically increases mortality risk when combined with other conditions. Current classifications fail to reflect the molecular drivers of PH, leaving treatment gaps. Synhale's approach with Telaglenastat targets elevated glutaminase activity, a key driver of vascular, cardiac, and pulmonary pathology, potentially benefiting not only rare Pulmonary Arterial Hypertension (Group 1) and chronic thromboembolic disease (Group 4) but also more prevalent PH linked to heart failure (Group 2) and chronic lung disease (Group 3). Telaglenastat, previously dosed in over 800 patients during oncology development, is Phase 2-ready with extensive preclinical data for PH. Synhale's clinical advancement strategy addresses an estimated $12B-$24B market opportunity across PH Groups 1-4. "We are embarking on our next round of fundraising to advance Telaglenastat through critical clinical milestones," added Holland. "Our virtual operating model enables us to be capital-efficient while maintaining world-class expertise focused on delivering breakthrough therapies for PH patients." About Synhale Therapeutics Synhale Therapeutics Inc. is a virtual biotech company dedicated to transforming Pulmonary Hypertension treatment by targeting elevated glutaminase activity—a key driver of vascular stiffness, fibrosis, and proliferation. Synhale's mission is to redefine PH treatment through mechanism-driven therapies that address the root cause of this disease. For Media & Investor Inquiries: Chad D. Holland [email protected] 617-758-8643 SOURCE Synhale Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

并购临床2期

2025-04-28

·PRNewswire

2025 AACR | Abbisko Therapeutics Presents Late-Breaking Pre-clinical Research Results on ABSK112 (EGFR exon20ins), ABSK131 (PRMT5*MTA), and ABK-KRAS-1

SHANGHAI, April 27, 2025 /PRNewswire/ -- Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics 02256.HK) today announced that it has presented four late-breaking pre-clinical research posters at the 2025 AACR conference held in Chicago, Illinois (USA) from April 25 to April 30. Results were shared for ABSK112 (EGFR exon20ins inhibitor), ABSK131 (PRMT5*MTA inhibitor), and ABK-KRAS-1 (pan-KRAS inhibitor), as well as results from a study investigating potential resistance mechanisms to KRAS G12C inhibitors. Abbisko presented the following posters at the 2025 AACR: Title1: Preclinical Evaluation of ABSK112, a Selective and CNS-penetrant Compound with Strong HER2 Inhibitory Activity for Treating HER2-Driven Solid Tumors Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 2 Session Date and Time: April 28, 2025, 2:00 PM - 5:00 PM (CDT) Location: Poster Section 54 Poster Board Number: 14 Poster Number: LB240 Conclusion: Our findings establish ABSK112 as a potent, selective and CNS-penetrant HER2 inhibitor, warranting further clinical evaluation of it as a monotherapy or in combination with HER2-targeted ADCs for the treatment of HER2+ cancers with brain metastases. Title 2: Loss-of-Function (LoF) of KEAP1 promotes cell survival through multiple mechanisms, leading to resistance to KRAS G12C inhibitors Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 3 Session Date and Time: April 29, 2025 9: 00AM – 12: 00 PM (CDT) Location: Poster Section 52 Poster Board Number: 1 Poster Number: LB278 Conclusion: KEAP1 LoF mutant NSCLCs develop resistance to KRAS G12C inhibitors through reduced drug-induced ROS accumulation, metabolic adaptation, and sustained activation of MAPK and AKT signaling. Combination therapies targeting glutamine metabolism (e.g., GLS1 inhibitors), MAPK (e.g., MEK inhibitors), and PI3K-AKT-mTOR pathways (e.g., BEZ235) reverse resistance and improve therapeutic efficacy in KEAP1-mutant cell lines. These strategies may restore sensitivity to KRAS G12C inhibitors and enhance clinical outcomes. Title 3: The MTA-Cooperative PRMT5 Inhibitor ABSK131 Exhibits Potent Activity and Broad Synergistic Potential in MTAP-Deleted Cancer Models Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4 Session Date and Time: April 30, 2025 9:00 AM - 12:00 PM (CDT) Location: Poster Section 51 Poster Board Number: 9 Poster Number: LB427 Conclusion: ABSK131 exhibits strong anti-tumor activity in MTAP-deleted lung and pancreatic cancer models and synergizes effectively with multiple therapeutic agents. These findings support the continued clinical development of ABSK131 as both a monotherapy and in combination regimens for MTAP-deleted cancers. Title 4: Discovery and characterization of a highly potent and orally available small-molecule inhibitor for diverse KRAS mutations Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4 Session Date and Time: April 30, 2025 9:00 AM - 12:00 PM (CDT) Location: Poster Section 51 Poster Board Number: 13 Poster Number: LB431 Conclusion: Taken together, ABK-KRAS-1 exhibits broad in vitro activity against different KRAS mutations and induces dose-dependent tumor regression in KRAS mutated xenograft models. Moreover, ABK-KRAS-1 possesses favorable drug-like properties. Here, ABK-KRAS-1 is presented as a promising therapeutic candidate for the treatment of cancers harboring KRAS mutations. About Abbisko Therapeutics Founded in April 2016, Abbisko Therapeutics Co., Ltd. (HKEX: 02256.HK), is an oncology-focused biopharmaceutical company based in Shanghai that is dedicated to the discovery and development of innovative medicines to treat unmet medical needs in China and globally. The Company was established by a group of seasoned drug hunters with rich research & development and managerial expertise from top multinational pharmaceutical companies. Since its founding, Abbisko Therapeutics has built an extensive pipeline of innovative programs focused on precision oncology and immuno-oncology. Please visit for more information. SOURCE Abbisko WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

AACR会议

2025-04-28

·上海和誉生物医药科技有限公司

2025 AACR | 和誉医药展示了ABSK131(PRMT5*MTA)、ABK-KRAS-1等4项最新临床前研究成果

2025年4月28号，和誉医药（港交所代码：02256）宣布，其在4月25日至30日于美国芝加哥举行的2025年美国癌症研究协会（AACR）年会上以壁报的形式发布了四项最新的临床前研究结果。包括其自主研发的EGFR Exon20ins抑制剂ABSK112和PRMT5*MTA抑制剂ABSK131以及pan-KRAS抑制剂 ABK-KRAS-1，以及一项研究KRAS G12C抑制剂潜在耐药机制的最新临床前研究成果。和誉医药在此次AACR大会上展示的报告信息如下:标题1: Preclinical Evaluation of ABSK112, a Selective and CNS-penetrant Compound with Strong HER2 Inhibitory Activity for Treating HER2-Driven Solid Tumors壁报场次:最新突破性研究:实验性分子疗法2壁报展示位置：54展区，14号板报报告时间：2025年4月28日2:00PM-5:00PM（美国中部时间）壁报展示编号：LB240结论：我们的研究结果表明，ABSK112是一种具有高效、选择性强且可穿透中枢神经系统的HER2抑制剂，支持其作为单药治疗或与靶向HER2的ADCs联合使用，进一步在伴有脑转移的HER2阳性癌症患者中进行临床评估。标题2: Loss-of-Function (LoF) of KEAP1 promotes cell survival through multiple mechanisms, leading to resistance to KRAS G12C inhibitors壁报场次:最新突破性研究:实验性分子疗法3壁报展示位置：52展区，1号板报报告时间：2024年4月29日9:00AM - 12:00 PM（美国中部时间）壁报展示编号：LB278结论：我们的研究表明，KEAP1 功能缺失（LoF）突变的非小细胞肺癌（NSCLC）通过降低药物诱导的活性氧（ROS）积累、代谢适应以及持续激活 MAPK 和 AKT 信号通路等多种方式，对 KRAS G12C 抑制剂产生耐药性。靶向谷氨酰胺代谢（如 GLS1 抑制剂）、MAPK 通路（如 MEK 抑制剂）以及 PI3K-AKT-mTOR 通路（如 BEZ235）的联合治疗可逆转耐药性，并在 KEAP1 突变细胞系中提高治疗效果。这些策略有望恢复对 KRAS G12C 抑制剂的敏感性，并改善临床疗效。标题3: The MTA-Cooperative PRMT5 Inhibitor ABSK131 Exhibits Potent Activity and Broad Synergistic Potential in MTAP-Deleted Cancer Models壁报场次:最新突破性研究:实验性分子疗法4壁报展示位置：51展区，9号板报报告时间：2025年4月30日9:00AM-12:00PM（美国中部时间）壁报展示编号：LB427结论：ABSK131在MTAP纯合缺失的肺癌和胰腺癌模型中表现出显著的抗肿瘤活性，并与多种治疗药物存在较强的协同效应。研究成果为ABSK131在MTAP纯合缺失的肿瘤中以单药或者联合治疗方案的临床开发提供了有力支持。标题4: Discovery and characterization of a highly potent and orally available small-molecule inhibitor for diverse KRAS mutations壁报场次:最新突破性研究:实验性分子疗法4壁报展示位置：51展区，13号板报报告时间：2025年4月30日9:00AM-12:00PM（美国中部时间）壁报展示编号：LB431结论：ABK-KRAS-1在体外实验表现出对不同KRAS突变的广谱的活性，在KRAS突变肿瘤模型中能剂量依赖性地诱导肿瘤消退。此外，ABK-KRAS-1具有良好的成药性。因此ABK-KRAS-1可作为一款用于治疗携带KRAS突变癌症的非常有前景的治疗候选药物。2025 AACR | Abbisko Therapeutics Presents Late-Breaking Pre-clinical Research Results on ABSK112 (EGFR exon20ins), ABSK131 (PRMT5*MTA), and ABK-KRAS-1 (pan-KRAS)28 April 2025, Shanghai – Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics 02256.HK) today announced that it has presented four late-breaking pre-clinical research posters at the 2025 AACR conference held in Chicago, Illinois (USA) from April 25 to April 30. Results were shared for ABSK112 (EGFR exon20ins inhibitor), ABSK131 (PRMT5*MTA inhibitor), and ABK-KRAS-1 (pan-KRAS inhibitor), as well as results from a study investigating potential resistance mechanisms to KRAS G12C inhibitors.Abbisko presented the following posters at the 2025 AACR:Title 1: Preclinical Evaluation of ABSK112, a Selective and CNS-penetrant Compound with Strong HER2 Inhibitory Activity for Treating HER2-Driven Solid TumorsSession Category: Late-Breaking Research: Experimental and Molecular Therapeutics 2Session Date and Time: April 28, 2025, 2:00 PM - 5:00 PM (CDT)Location: Poster Section 54Poster Board Number: 14Poster Number: LB240Conclusion: Our findings establish ABSK112 as a potent, selective and CNS-penetrant HER2 inhibitor, warranting further clinical evaluation of it as a monotherapy or in combination with HER2-targeted ADCs for the treatment of HER2+ cancers with brain metastases.Title 2: Loss-of-Function (LoF) of KEAP1 promotes cell survival through multiple mechanisms, leading to resistance to KRAS G12C inhibitorsSession Title: Late-Breaking Research: Experimental and Molecular Therapeutics 3Session Date and Time: April 29, 2025 9: 00AM – 12: 00 PM (CDT)Location: Poster Section 52Poster Board Number: 1Poster Number: LB278Conclusion: KEAP1 LoF mutant NSCLCs develop resistance to KRAS G12C inhibitors through reduced drug-induced ROS accumulation, metabolic adaptation, and sustained activation of MAPK and AKT signaling. Combination therapies targeting glutamine metabolism (e.g., GLS1 inhibitors), MAPK (e.g., MEK inhibitors), and PI3K-AKT-mTOR pathways (e.g., BEZ235) reverse resistance and improve therapeutic efficacy in KEAP1-mutant cell lines. These strategies may restore sensitivity to KRAS G12C inhibitors and enhance clinical outcomes.Title 3: The MTA-Cooperative PRMT5 Inhibitor ABSK131 Exhibits Potent Activity and Broad Synergistic Potential in MTAP-Deleted Cancer ModelsSession Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4Session Date and Time: April 30, 2025 9:00 AM - 12:00 PM (CDT)Location: Poster Section 51Poster Board Number: 9Poster Number: LB427Conclusion: ABSK131 exhibits strong anti-tumor activity in MTAP-deleted lung and pancreatic cancer models and synergizes effectively with multiple therapeutic agents. These findings support the continued clinical development of ABSK131 as both a monotherapy and in combination regimens for MTAP-deleted cancers.Title 4: Discovery and characterization of a highly potent and orally available small-molecule inhibitor for diverse KRAS mutations Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4Session Date and Time: April 30, 2025 9:00 AM - 12:00 PM (CDT) Location: Poster Section 51Poster Board Number: 13Poster Number: LB431Conclusion: Taken together, ABK-KRAS-1 exhibits broad in vitro activity against different KRAS mutations and induces dose-dependent tumor regression in KRAS mutated xenograft models. Moreover, ABK-KRAS-1 possesses favorable drug-like properties. Here, ABK-KRAS-1 is presented as a promising therapeutic candidate for the treatment of cancers harboring KRAS mutations.关于和誉和誉医药（香港联交所代码：02256）成立于2016年，是一家立足中国，着眼全球的创新药研发公司。公司的创始人和管理团队拥有多年顶尖跨国药企的研发和管理经验，并参与了多个临床及上市新药的研发。和誉医药专注于肿瘤新药研发，以小分子肿瘤精准治疗和小分子肿瘤免疫治疗药物为核心，着眼病患及医药市场的需求，秉承国际新药开发的理念和标准，致力于开发新颖及高潜力药物靶点的潜在first-in-class或best-in-class创新药物，用于改善中国及全球病人的生活质量。自成立以来，和誉医药已经建立了丰富的创新产品管线，涵盖肿瘤精准治疗领域以及肿瘤免疫治疗领域。更多信息，欢迎访问 www.abbisko.com。

AACR会议临床结果突破性疗法抗体药物偶联物临床1期