预约演示
更新于：2026-06-23
Tersolisib
更新于：2026-06-23
概要
基本信息
药物类型 小分子化药 |
别名 STX-H1047-PI3Ka inhibitors (Scorpion Therapeutics)、LY4064809、ST-814 + [2] |
作用方式 抑制剂 |
作用机制 PIK3CA H1047R 抑制剂(PIK3CA H1047R突变 抑制剂)、PIK3CA H1047X 抑制剂(磷脂酰肌醇3-激酶α突变型H1047X 抑制剂) |
在研适应症 |
非在研适应症- |
非在研机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)临床3期 |
特殊审评- |
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结构/序列
分子式C16H12F5N5O2 |
InChIKeyLGPNQALKGDDVBD-CYBMUJFWSA-N |
CAS号2883540-92-7 |
关联
7
项与 Tersolisib 相关的临床试验NCT07519525
A Phase 1, Open-label Study of the Absolute Bioavailability of [14C]-LY4064809 in Healthy Adult Participants
NCT07339735
A Phase 1, Open-Label Study to Assess the Relative Bioavailability of Two LY4064809 Formulations in Healthy Adult Participants
NCT07174336
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY4064809 Combined With a CDK4/6 Inhibitor and Endocrine Therapy in Adults With HR+, HER2-Advanced Breast Cancer With a PIK3CA Mutation Who Received No Prior Treatment for Advanced Breast Cancer (PIKALO-2)
100 项与 Tersolisib 相关的临床结果
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100 项与 Tersolisib 相关的转化医学
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100 项与 Tersolisib 相关的专利（医药）
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8
项与 Tersolisib 相关的文献（医药）2026-08-01EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Benzothiophene-based, orally active PIK3CA H1047R mutant-selective inhibitors for the treatment of HR+/HER2- breast cancer
Article
作者: Xu, Hang ; Jin, Lei ; Yang, Fanglong ; Wang, Siqin ; Jia, Xiangyu ; Fan, Xing ; Xia, Yuanfeng ; Zhao, Sheng ; Lu, Biao
PI3Kα plays a key role in a variety of cellular processes, and its gene mutations are closely related to the occurrence and development of many types of cancer. Although two orthosteric PI3Kα inhibitors including Alpelisib and Inavolisib have been launched onto market, they often cause toxic and side effects due to insufficient selectivity for PIK3CA mutant protein. The development of allosteric PI3Kα inhibitors provides new ideas for overcoming these problems. Our research focuses on optimizing a novel series of allosteric PI3Kα inhibitors derived from STX-478. By integrating scaffold hopping and comprehensive structural modification strategies, we obtained the lead compound allosteric PI3Kα inhibitor 11f with a benzothiophene scaffold. The inhibitor demonstrates high selectivity for PIK3CA mutant protein, low hERG inhibition, minimal CYP inhibition, excellent in vivo efficacy, good safety and no impact on insulin balance. Collectively, these findings confirm that compound 11f is a highly promising drug candidate for the targeted therapy of PIK3CA H1047R mutant HR+/HER2-breast cancer.
2026-01-23Annual Review of Pharmacology and Toxicology
Structural Insights into the Development of Inhibitors Against Cancer-Specific Mutations of PI3Kα
Review
作者: Liu, Xiao ; Chen, Yan ; Feng, Wenbo ; Zhou, Qingtong ; Chen, Yanyan ; Han, Wei ; Wang, Ming-Wei
Phosphoinositide 3-kinase alpha (PI3Kα) is a pivotal regulator of cell growth, proliferation, and survival. Dysregulation of the PI3K/AKT/mTOR pathway, driven predominantly by
PIK3CA
mutations (e.g., H1047R, E542K, and E545K), is a hallmark of many cancers. Advances in structural, biochemical, and computational studies have elucidated mutation-specific conformational changes of PI3Kα. While early pan- and isoform-selective PI3K inhibitors (alpelisib) show clinical utility, their intrinsic toxicity and resistance to treatment persist. Recent breakthroughs include the emergence of allosteric inhibitors (RLY-2608 and STX-478) that exploit mutation-induced cryptic pockets to achieve mutant selectivity as well as covalent inhibitors and degraders (inavolisib) that enhance specificity, aiming at decoupling antitumor activity from metabolic dysfunction. This review synthesizes current progress in PI3Kα inhibitor development, emphasizing structural characteristics, clinical challenges, and emerging strategies. Addressing challenges to increase mutant selectivity, exploring conformational modulation, uncovering new mechanisms of action, and implementing personalized therapies are key future directions for PI3Kα-targeted drug discovery.
2025-08-10BRITISH JOURNAL OF CANCER
Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models
Article
作者: Cantley, Lewis C ; Mukherjee, Siddhartha ; Maddocks, Oliver D K ; Goncalves, Marcus D ; Tyrakis, Petros A ; Kampjut, Domen ; Lindström, H Jonathan G ; Hopkins, Benjamin D ; Chirnomas, Deborah ; Steele, Georgina F
Abstract:
Background:
While PI3K/AKT/mTOR signalling plays a critical role in cancer, targeting this pathway with single node inhibitors has limited efficacy due to several known factors such as pathway feedback reactivation, co-occurring pathway mutations, and systemic glucose dysregulation leading to hyperinsulinemia. While multi-node inhibition approaches have shown promising clinical efficacy, they require further mechanistic characterisation.
Methods:
Using models of endometrial and breast cancer, we evaluated the efficacy of a multi-node PI3K/AKT/mTOR pathway inhibitor approach utilising the dual mTORC1/mTORC2 inhibitor sapanisertib, PI3Kα inhibitor serabelisib and an insulin-supressing diet. Pathway signalling inhibition versus a range of single-node inhibitors was measured via S6, AKT and 4E-BP1 phosphorylation.
Results:
The serabelisib-sapanisertib combination more effectively suppressed PI3K/AKT/mTOR pathway signalling, particularly 4E-BP1, than single-node inhibitors, including alpelisib, capivasertib, inavolisib, everolimus and mutant-specific PI3K inhibitors RLY-2608 and STX-478. Serabelisib plus sapanisertib combined effectively with a range of other therapeutics, such as chemotherapies, hormone targeted therapies and CDK4/6 inhibitors. In xenograft models, sapanisertib, serabelisib plus paclitaxel/insulin supressing diet achieved complete inhibition of tumour growth/tumour regression.
Conclusion:
Multi-node PI3K/AKT/mTOR pathway inhibition with serabelisib, sapanisertib and ISD is highly effective in preclinical models of endometrial and breast cancer, supporting continued clinical development in these and other solid tumours.
100 项与 Tersolisib 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 晚期乳腺癌 | 临床3期 | 美国 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 中国 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 日本 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 阿根廷 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 澳大利亚 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 比利时 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 巴西 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 加拿大 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 法国 | 2025-12-22 | |
| 晚期乳腺癌 | 临床3期 | 德国 | 2025-12-22 |
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临床结果
临床结果
适应症
分期
评价
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临床1/2期 | 晚期恶性实体瘤 PIK3CA mutant | HR+ | HER2- | 193 | 鹹壓製窪繭範築簾壓顧(願衊醖選網鬱憲積壓觸) = 鑰築網鑰壓遞艱鏇願齋 窪範顧壓鬱鹽糧積願獵 (艱膚獵鹽醖積願網憲觸 ) 更多 | 积极 | 2026-05-29 | ||
鹹壓製窪繭範築簾壓顧(願衊醖選網鬱憲積壓觸) = 衊築鹽膚壓夢醖構簾鑰 窪範顧壓鬱鹽糧積願獵 (艱膚獵鹽醖積願網憲觸 ) 更多 | |||||||
临床1/2期 | 晚期恶性实体瘤 PIK3CA mutations | HR+ | HER2- | 204 | 蓋醖壓蓋窪觸積窪積選(衊蓋範選鹽鏇積壓範遞) = 窪襯蓋窪夢構艱淵夢網 獵餘築壓淵艱艱鑰襯鏇 (鹹糧艱襯壓網願顧醖艱 ) 更多 | 积极 | 2025-10-17 | ||
蓋醖壓蓋窪觸積窪積選(衊蓋範選鹽鏇積壓範遞) = 繭醖網艱廠襯積繭憲蓋 獵餘築壓淵艱艱鑰襯鏇 (鹹糧艱襯壓網願顧醖艱 ) 更多 | |||||||
临床1/2期 | 晚期恶性实体瘤 PI3Kαm | 61 | 鏇鏇糧夢觸鬱鏇遞繭鬱(齋餘襯醖醖衊範廠鹹繭) = 鹽獵選襯網築遞蓋膚艱 襯艱鏇艱範選鏇築衊鑰 (繭廠襯範鬱鬱顧鑰簾醖 ) 更多 | 积极 | 2024-09-15 | ||
(HR+/HER2- BC) | 構餘壓鑰鹽選簾選觸蓋(觸醖鬱願選網顧憲蓋選) = 糧窪顧醖憲積窪積鏇鹹 衊衊鹹網壓構壓壓壓蓋 (鑰衊襯選觸鬱餘顧鏇範 ) |
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