色雷利塞(Serabelisib) - 药物靶点：PI3Kα_在研适应症：子宫内膜样腺癌，复发性子宫内膜癌，HER2 阴性乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

6-(2-Aminobenzo[d]oxazol-5-yl)imidazo [1,2-a]pyridine-3-yl morpholinomethanone、MLN1117、AGN-PC-0DB6FL

+ [5]

靶点

PI3Kα

作用方式

抑制剂

作用机制

PI3Kα抑制剂(磷脂酰肌醇3-激酶α抑制剂)

治疗领域

肿瘤泌尿生殖系统疾病皮肤和肌肉骨骼疾病+ [3]

在研适应症

子宫内膜样腺癌复发性子宫内膜癌HER2 阴性乳腺癌+ [5]

非在研适应症

晚期癌症晚期恶性实体瘤结直肠癌+ [11]

原研机构

Takeda Pharmaceutical Co., Ltd.

在研机构

University HospitalTakeda Pharmaceuticals International, Inc.

Kaken Pharmaceutical Co., Ltd.

+ [2]

非在研机构

Petra Pharma Corp.

Millennium Pharmaceuticals, Inc.

Takeda Pharmaceutical Co., Ltd.

权益机构

Petra Pharma Corp.

Takeda Pharmaceutical Co., Ltd.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)、孤儿药 (欧盟)、孤儿药 (日本)

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结构/序列

分子式C19H17N5O3

InChIKeyBLGWHBSBBJNKJO-UHFFFAOYSA-N

CAS号1268454-23-4

关联

13

项与色雷利塞相关的临床试验

NCT07558733

/ Recruiting临床1/2期

Open-Label Umbrella Study to Evaluate Safety and Efficacy of Sapanisertib and Serabelisib (PIKTOR) in Various Combinations in Patients With HR+/HER2- Advanced or Metastatic Breast Cancer

The study is a Phase 1b/2, multi-center, open-label, dose escalation trial evaluating the safety and preliminary efficacy of sapanisertib and serabelisib (PIKTOR) with fulvestrant and/or other anticancer therapies in participants with HR+/HER2- advanced/metastatic breast cancer.

开始日期2026-04-22

申办/合作机构

Faeth Therapeutics LLC

NCT06463028

/ Recruiting临床2期

An Open-label, Multi-Center, Phase 2 Clinical Trial Evaluating Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel, and a Substudy Evaluating PIKTOR With Paclitaxel Plus an Insulin-Suppressing Diet, in Patients With Advanced or Recurrent Endometrial Cancer

This is a Phase 2, multicenter, open-label, single-arm study to evaluate the efficacy and safety of sapanisertib and serabelisib (PIKTOR) with paclitaxel in participants with advanced or recurrent endometrial cancer.

开始日期2024-12-12

申办/合作机构

Faeth Therapeutics LLC

NCT05300048

/ Terminated临床1期

A Phase 1b Study of Serabelisib in Combination With an Insulin Suppressing Diet (Study ISD) and With or Without Nab-paclitaxel in Adult Subjects With Advanced Solid Tumors With PIK3CA Mutations With or Without PTEN Loss

This study will evaluate the feasibility of optimizing the safety and tolerability of serabelisib (an investigational PI3K inhibitor) when combined with an ISD and with or without nab-paclitaxel with a goal of reducing side effects and enhancing anticancer activity.

开始日期2022-04-22

申办/合作机构

Faeth Therapeutics LLC

100 项与色雷利塞相关的临床结果

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100 项与色雷利塞相关的转化医学

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100 项与色雷利塞相关的专利（医药）

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23

项与色雷利塞相关的文献（医药）

2026-02-12·JOURNAL OF MEDICINAL CHEMISTRY

From Hit to Lead: Discovery of Novel Selective RIPK1 Inhibitor with Pyridoimidazole Scaffold for the Treatment of Autoimmune Diseases through Phenotypic Screening and Structural Optimization

Article

作者: Ding, Yang ; Hu, Zixin ; Zhao, Yongfang ; Kang, Xinyi ; Yan, Huanren ; Zhao, Yan ; Ma, Youzhen ; Liu, Zhiyi ; Geng, Zixiang ; Tang, Mei-Lin ; Yuan, Benjun ; Fan, Rui ; Xu, Han-Chen ; Li, Fuzhuo ; Sun, Nannan ; Chen, Yibo ; Dorothy Wong, Zhi Ying ; Lin, Ze-Min ; Xiong, Xiao-Yu ; He, Dong-Yi ; Zuo, Jian-Ping ; Min, Delin ; Wan, Jihong

Autoimmune diseases remain challenging to treat due to the limitations of TNFα-targeted biologics and the inefficacy of small molecules directly targeting TNFα. RIPK1, a central mediator of TNFα-driven inflammation and necroptosis, offers a promising alternative therapeutic target. Using drug repurposing and phenotype-based high-content screening of 378 clinical-stage kinase inhibitors, TAK-117 (a PI3Kα inhibitor) was identified as a RIPK1 hit compound with a novel pyridoimidazole scaffold. Guided by structure-based optimization and four iterative SAR cycles, WJH-C19 was developed, exhibiting >1000-fold increased RIPK1 potency (IC₅₀ = 5.7 nM) and negligible PI3Kα activity (IC₅₀ > 10 μM). Mechanistically, WJH-C19 suppressed the RIPK1/RIPK3/MLKL signaling axis, attenuating inflammatory responses. Oral administration of WJH-C19 achieved robust efficacy in DSS-induced colitis and CFA-induced arthritis models, with favorable pharmacokinetics and no observable toxicity. These results establish WJH-C19 as a potent lead and highlight the pyridoimidazole scaffold as a privileged chemotype for RIPK1-targeted drug discovery in autoimmune diseases.

2025-08-10·BRITISH 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: Mukherjee, Siddhartha ; Cantley, Lewis C ; 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.

2025-08-01·MOLECULAR DIVERSITY

iDCNNPred: an interpretable deep learning model for virtual screening and identification of PI3Ka inhibitors against triple-negative breast cancer

Article

作者: Jaiswal, Ravishankar ; Siddiqi, Mohammad Imran ; Bhati, Girdhar ; Ahmed, Shakil

Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 expression, accounting for 15-20% of breast cancer cases. It is challenging due to low therapeutic response, heterogeneity, and aggressiveness. The PI3Ka isoform is a promising therapeutic target, often hyperactivated in TNBC, contributing to uncontrolled growth and cancer cell formation. We have proposed an interpretable deep convolutional neural network prediction (iDCNNPred) system using 2D molecular images to classify bioactivity and identify potential PI3Ka inhibitors. We built Custom-DCNN models and pre-trained models such as AlexNet, SqueezeNet, and VGG19 by using the Bayesian optimization algorithm, and found that our Custom-DCNN model performed better than a pre-trained model with lower complexity and memory usage. All top-performed models were screened with the Maybridge Chemical library to find predictive hit molecules. The screened molecules were further evaluated for protein-ligand interaction with molecular docking and finally 12 promising hits were shortlisted for biological validation using in-vitro PI3K inhibition studies. After biological evaluation, 4 potent molecules with different structural moieties were identified, and these molecules present new starting scaffolds for further improvement in terms of their potency and selectivity as PI3K inhibitors with the help of medicinal chemistry efforts. Furthermore, we also showed the significance of the interpretation and visualization of the model's predictions by the Grad-CAM technique, enhancing the robustness, transparency, and interpretability of the model's predictions. The data and script files and prediction run of models used for this study to reproduce the experiment are available in the GitHub repository at https://github.com/ravishankar1307/iDCNNPred.git .

28

项与色雷利塞相关的新闻（医药）

2026-08-28

·Business Wire

Faeth Therapeutics Announces Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

AUSTIN, Texas--(BUSINESS WIRE)--Faeth Therapeutics, Inc. (Nasdaq: FTH) today announced that the Compensation Committee of Faeth’s Board of Directors granted three new employees options to purchase an aggregate of 94,000 shares of the Company’s common stock in connection with their employment (collectively, the “Option Awards”). The Option Awards were granted effective August 25, 2026, pursuant to the Company’s 2026 Inducement Plan as a material inducement to the individuals entering employment with Faeth in accordance with Nasdaq Listing Rule 5635(c)(4). The Option Awards have an exercise price of $34.52 per share, equal to the closing price of the Company’s common stock on the grant date. The Option Awards will vest, with respect to 25% of the shares subject to each such award, on the first anniversary of the applicable employee’s start date, with the remaining shares vesting in 36 substantially equal monthly installments thereafter, in each case subject to such employee’s continued service with Faeth through each such vesting date. The Option Awards have a term of ten years from the grant date and are otherwise subject to the terms and conditions of the 2026 Inducement Plan and the applicable award agreement. About Faeth Therapeutics Faeth Therapeutics, Inc. (Nasdaq: FTH) is a clinical-stage biotechnology company focused on improving outcomes for cancer patients through multi-node inhibition of critical oncogenic pathways. The Company’s lead program is PIKTOR, an investigational all-oral combination of serabelisib and sapanisertib in development for endometrial and breast cancer. Faeth was co-founded in 2019 by Anand Parikh and Oliver Maddocks, Ph.D., together with scientific founders Lewis Cantley, Ph.D., the discoverer of the PI3K pathway; Siddhartha Mukherjee, M.D., D.Phil.; Karen Vousden, Ph.D.; Scott Lowe, Ph.D.; and Greg Hannon, Ph.D. The Company intends to use its website as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD. For more information, please visit www.faeththerapeutics.com and follow the Company on LinkedIn.

2026-08-18

·Pharmaceutical Technology

Faeth’s PIKTOR plus paclitaxel combo gains FDA fast track status

Faeth Therapeutics is conducting a Phase II trial, Study FTH-PIK-201, in second-line advanced endometrial cancer. Credit: Jo Panuwat D / Shutterstock.com. Faeth Therapeutics has received the US Food and Drug Administration’s (FDA) fast track designation for the sapanisertib and serabelisib (PIKTOR) with paclitaxel combination to treat advanced or recurrent endometrial cancer. The designation applies specifically to patients whose tumours contain a phosphatidylinositol 3-kinase / protein kinase B / mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway alteration. It also applies to those who have previously undergone platinum-based chemotherapy and an immune checkpoint inhibitor. Faeth Therapeutics is currently conducting a Phase II trial of this treatment approach, known as Study FTH-PIK-201, in second-line advanced endometrial cancer. The company anticipates releasing top line results from this trial by the end of this year. Faeth Therapeutics CEO Anand Parikh said: “Fast track designation for PIKTOR reflects the significant unmet need in advanced endometrial cancer for patients whose disease has progressed despite platinum-based chemotherapy and an immune checkpoint inhibitor. “We believe PIKTOR’s multi-node approach to the PI3K/AKT/mTOR pathway is well suited to this population as our preclinical data suggests that PIKTOR can resensitise patients to chemotherapy.” PIKTOR is described as an investigational, all-oral combination therapy and is designed to inhibit several nodes of the PI3K/AKT/mTOR pathway, which, according to published literature, is altered in up to half of all solid tumours. In addition to the endometrial cancer trial, PIKTOR is being tested in a Phase Ib/II study for hormone receptor positive / human epidermal growth factor receptor 2 negative (HR+/HER2-) advanced breast cancer, referred to as Study FTH-PIK-101. The first patient in this study was dosed in April, with interim results expected in 2027. Faeth Therapeutics focuses on multi-node therapies for cancer, with PIKTOR as its leading development programme.

快速通道临床2期免疫疗法

2026-08-18

·allsci.com

Faeth's PIKTOR combo gets FDA fast track for biomarker-selected endometrial cancer

Austin, Texas-based Faeth Therapeutics (Nasdaq: FTH) announced receipt of US FDA Fast Track Designation for sapanisertib and serabelisib (PIKTOR) in combination with paclitaxel for patients with advanced or recurrent endometrial cancer whose tumors harbor a PI3K/AKT/mTOR pathway alteration and who have previously received platinum-based chemotherapy and an immune checkpoint inhibitor (ICI). PIKTOR is an all-oral combination of serabelisib, a selective PI3K-alpha inhibitor, and sapanisertib, a dual mTORC1/mTORC2 inhibitor, designed to block multiple nodes of the PI3K/AKT/mTOR pathway simultaneously. The designation applies to a population with limited post-ICI options and is supported by Phase 1b data from NCT03154294, in which PIKTOR plus paclitaxel produced an 80% overall response rate (ORR) in patients with advanced endometrioid endometrial cancer — comprising three complete responses and one partial response in five evaluable patients — and a median progression-free survival of 11 months against a historical chemotherapy benchmark of three to four months. No p-value was reported given the small sample size. Across the broader Phase 1b cohort of 15 response-evaluable patients with mixed solid tumors, the ORR was 47%, rising to 71% in patients with confirmed PI3K pathway mutations. These data directly underpin the ongoing Phase II trial FTH-PIK-201 (GOG-3111), a multicenter, open-label, single-arm study of approximately 40 patients with second-line advanced endometrial cancer, which enrolled its first patient in March 2025. Fast Track status enables more frequent FDA interactions and rolling review, and Faeth has said it expects topline data from FTH-PIK-201 by year-end 2026. Neither sapanisertib nor serabelisib has received marketing authorization from the FDA, the European Medicines Agency, or any other major regulator for any indication. The Fast Track designation is the most advanced regulatory milestone either molecule has achieved. Faeth is also running a Phase Ib/II trial in hormone receptor-positive, HER2-negative advanced breast cancer (Study FTH-PIK-101, NCT07558733), with the first patient dosed in April 2026 and interim data anticipated in 2027. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article

临床结果快速通道免疫疗法临床1期临床2期

100 项与色雷利塞相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14935

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HER2 阴性乳腺癌	临床2期	美国	Faeth Therapeutics LLC	2026-04-22
HR阳性/HER2阴性乳腺癌	临床2期	美国	Faeth Therapeutics LLC	2026-04-22
HER2阳性转移性乳腺癌	临床2期	美国	Faeth Therapeutics LLC	2026-04-22
子宫内膜样腺癌	临床2期	美国	Faeth Therapeutics LLC	2024-12-12
结直肠癌	临床2期	-	Petra Pharma Corp.	2020-09-01
子宫内膜癌	临床2期	-	Petra Pharma Corp.	2020-09-01
头颈部肿瘤	临床2期	-	Petra Pharma Corp.	2020-09-01
局部晚期恶性实体瘤	临床2期	-	Petra Pharma Corp.	2020-09-01
肺癌	临床2期	-	Petra Pharma Corp.	2020-09-01
PIK3CA突变的乳腺癌	临床2期	-	Petra Pharma Corp.	2020-09-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03154294 (CTgov)	临床1期	晚期恶性实体瘤	19	paclitaxel+TAK-117+TAK-228 (Cohort 1)	蓋餘壓獵積構顧襯鹽網 = 築襯醖餘網廠糧築襯積願積衊鬱鏇鑰範齋積淵 (襯蓋膚襯淵窪構網構製, 積衊鹽廠廠顧醖齋壓範 ~ 糧構廠廠鏇製範憲鹽願) 更多	-	2024-07-26
				paclitaxel+TAK-117+TAK-228 (Cohort 2)	蓋餘壓獵積構顧襯鹽網 = 鬱獵艱襯鹽齋醖糧範膚願積衊鬱鏇鑰範齋積淵 (襯蓋膚襯淵窪構網構製, 鹹襯鑰積壓蓋鬱餘積餘 ~ 齋餘選顧選簾窪壓積鹹) 更多
NCT03193853 (CTgov)	临床2期	转移性三阴性乳腺癌	12	Nab Paclitaxel+Cisplatin+Tak-117+Tak-228	鹹繭範鑰鹹鬱鹹遞襯願 = 觸蓋鏇簾餘鑰簾鑰積遞膚窪壓窪製範遞艱構積 (遞壓構糧齋範夢觸選蓋, 遞網艱淵鬱廠淵積衊襯 ~ 夢選構願遞壓獵獵鏇夢) 更多	-	2023-05-09
NCT03154294 (ASCO 12021 \| ASCO 22021) 人工标引	临床1期	卵巢癌 \| 子宫内膜癌 \| 乳腺癌 PI3K Mutation \| AKT Mutation \| MTOR Mutation	19	paclitaxel+sapanisertib+serabelisib	蓋築醖築鏇艱製獵積網(製糧憲築遞顧艱鹽醖簾) = 獵範網衊鬱齋淵製願積願構壓鹹遞網糧膚遞餘 (構膚餘範憲製窪製簾遞 ) 更多	积极	2021-05-20
NCT02724020 (CTgov)	临床2期	转移性透明细胞性肾细胞癌	96	everolimus (Arm A: Single-agent Everolimus 10 mg QD)	壓膚糧遞觸膚窪醖積齋(鹹蓋憲糧衊衊鏇獵齋鬱) = 膚觸齋網廠獵餘遞膚遞齋鹹壓鹽衊廠憲鹽獵糧 (膚鏇鑰構構顧膚壓餘醖, 顧獵製鏇構網顧構廠鑰 ~ 窪蓋蓋範襯膚顧選壓鬱) 更多	-	2021-02-21
				MLN0128 (Arm B: Single-agent MLN0128 30 mg QW)	壓膚糧遞觸膚窪醖積齋(鹹蓋憲糧衊衊鏇獵齋鬱) = 鹽獵網鬱築壓蓋壓鹹築齋鹹壓鹽衊廠憲鹽獵糧 (膚鏇鑰構構顧膚壓餘醖, 遞壓鏇夢範鹽淵觸餘淵 ~ 襯醖範築餘壓夢襯鏇膚) 更多
NCT02725268 (phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer, CTgov)	临床2期	复发性子宫内膜癌	241	Paclitaxel (Paclitaxel 80 mg/m^2)	選鏇觸鏇壓遞憲鏇窪繭(繭糧鑰夢壓遞網鑰製壓) = 壓鏇蓋糧繭製鹹遞鏇製觸淵觸構壓憲範鹹顧構 (艱鬱積夢積壓壓築積獵, 糧齋醖壓鏇艱觸製壓襯 ~ 餘襯觸簾襯壓糧繭壓襯) 更多	-	2020-06-09
				Paclitaxel+Sapanisertib (Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg)	選鏇觸鏇壓遞憲鏇窪繭(繭糧鑰夢壓遞網鑰製壓) = 範糧餘窪淵餘鹹網糧築觸淵觸構壓憲範鹹顧構 (艱鬱積夢積壓壓築積獵, 膚糧壓網築醖齋鹹觸選 ~ 鏇鏇鏇範積觸獵壓製遞) 更多
NCT02551055 (CTgov)	临床1期	胃腺癌 \| 转移性胃食管腺癌	32	Alisertib+MLN1117 (MLN1117 300 mg + Alisertib)	衊廠艱鏇夢廠憲積淵衊 = 顧築網觸淵鹹齋襯壓憲網憲鏇衊願齋繭膚鬱構 (鹹積膚鏇窪網鹹蓋構遞, 網製繭遞窪窪選廠觸範 ~ 鏇醖鹹鏇壓範醖醖網廠) 更多	-	2019-09-20
				Alisertib+MLN1117 (MLN1117 600 mg + Alisertib)	衊廠艱鏇夢廠憲積淵衊 = 顧遞鑰範製範膚積憲鏇網憲鏇衊願齋繭膚鬱構 (鹹積膚鏇窪網鹹蓋構遞, 獵獵醖簾齋願壓範獵膚 ~ 築顧願餘觸憲襯艱淵蓋) 更多
NCT02393209 (CTgov)	临床1/2期	转移性非小细胞肺癌	14	Docetaxel+TAK-117 (Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2)	構膚襯鏇淵壓鹹醖窪夢 = 膚鹹築廠選夢艱襯觸淵鬱鏇蓋壓齋鹹鹹鏇衊壓 (蓋鏇獵膚鹹廠築壓繭積, 窪醖構憲糧獵獵醖積夢 ~ 餘築夢繭顧願鹽製構遞) 更多	-	2018-02-07
				Docetaxel+TAK-117 (Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2)	構膚襯鏇淵壓鹹醖窪夢 = 鏇窪鹹範鹹衊廠願獵遞鬱鏇蓋壓齋鹹鹹鏇衊壓 (蓋鏇獵膚鹹廠築壓繭積, 範構醖製糧遞糧襯範鹽 ~ 遞築襯蓋壓餘願壓範遞) 更多
NCT01449370 (ASCO2015)	临床1期	晚期恶性实体瘤	76	MLN1117 once daily (QD)	製鑰積願鑰鏇獵膚築齋(窪淵觸觸繭積襯鹽憲網) = 鹽齋範簾餘網遞鑰鹽餘醖獵鏇齋願齋膚觸壓築 (範觸壓鑰鏇餘淵顧蓋廠 ) 更多	-	2015-05-20
				MLN1117 3 days per week (MWF)	製鑰積願鑰鏇獵膚築齋(窪淵觸觸繭積襯鹽憲網) = 襯範構鹹繭觸顧蓋窪製醖獵鏇齋願齋膚觸壓築 (範觸壓鑰鏇餘淵顧蓋廠 ) 更多