Delving into the Latest Updates on Serabelisib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

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

+ [5]

Target

PI3Kα

Action

inhibitors

Mechanism

PI3Kα inhibitors(Phosphatidylinositol 3 kinase alpha inhibitors)

Therapeutic Areas

NeoplasmsUrogenital DiseasesSkin and Musculoskeletal Diseases+ [3]

Active Indication

Endometrial Endometrioid AdenocarcinomaRecurrent Endometrial CancerHER2-negative breast cancer+ [5]

Inactive Indication

Advanced cancerAdvanced Malignant Solid NeoplasmColorectal Cancer+ [11]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

University HospitalTakeda Pharmaceuticals International, Inc.

Kaken Pharmaceutical Co., Ltd.

+ [2]

Inactive Organization

Petra Pharma Corp.

Millennium Pharmaceuticals, Inc.

Takeda Pharmaceutical Co., Ltd.

License Organization

Petra Pharma Corp.

Takeda Pharmaceutical Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (United States), Orphan Drug (European Union), Orphan Drug (Japan)

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Structure/Sequence

Molecular FormulaC19H17N5O3

InChIKeyBLGWHBSBBJNKJO-UHFFFAOYSA-N

CAS Registry1268454-23-4

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

10 Aug 2025·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

Author: Mukherjee, Siddhartha ; Cantley, Lewis C ; Goncalves, Marcus D ; Maddocks, Oliver D K ; 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.

01 Aug 2025·MOLECULAR DIVERSITY

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

Article

Author: 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 .

22

News (Medical) associated with Serabelisib

28 Aug 2026

·www.businesswire.com

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.

28 Aug 2026

·www.biospace.com

Faeth Therapeutics Announces Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) - August 28, 2026

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 and follow the Company on LinkedIn. Contacts Investor Contact: Matthew Biegler, SVP, Investor Relations matt@faeththerapeutics.com Media Contact: Patrick Schmidt, Consort Partners faeththerapeutics@consortpartners.com

18 Aug 2026

·www.pharmaceutical-technology.com

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.

Fast TrackPhase 2Immunotherapy

100 Deals associated with Serabelisib

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14935

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HER2-negative breast cancer	Phase 2	United States	Faeth Therapeutics LLC	22 Apr 2026
Hormone receptor positive HER2 negative breast cancer	Phase 2	United States	Faeth Therapeutics LLC	22 Apr 2026
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Phase 2	United States	Faeth Therapeutics LLC	22 Apr 2026
Endometrial Endometrioid Adenocarcinoma	Phase 2	United States	Faeth Therapeutics LLC	12 Dec 2024
Colorectal Cancer	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Endometrial Carcinoma	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Head and Neck Neoplasms	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Locally Advanced Malignant Solid Neoplasm	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Lung Cancer	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
PIK3CA mutant Breast Cancer	Phase 2	-	Petra Pharma Corp.	01 Sep 2020

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03154294 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	19	paclitaxel+TAK-117+TAK-228 (Cohort 1)	nfvhltovhw = wxlmdfsntx xhfmuutrks (ujagfzdiqh, eqtzjtzqll - iatdqrhdrc) View more	-	26 Jul 2024
				paclitaxel+TAK-117+TAK-228 (Cohort 2)	nfvhltovhw = jncstujuhl xhfmuutrks (ujagfzdiqh, helmguokzc - bhfdyxdren) View more
NCT03193853 (CTgov)	Phase 2	Metastatic Triple-Negative Breast Carcinoma	12	Nab Paclitaxel+Cisplatin+Tak-117+Tak-228	kqyempsdyt = oxobsdpcxu nmljgxteki (trtvregzfm, dzzhdqvqwz - olufyfnlem) View more	-	09 May 2023
NCT03154294 (ASCO 12021 \| ASCO 22021) Manual	Phase 1	Ovarian Cancer \| Endometrial Carcinoma \| Breast Cancer PI3K Mutation \| AKT Mutation \| MTOR Mutation	19	paclitaxel+sapanisertib+serabelisib	kdscnmqliv(kgswhqewio) = vfbpqanzex yxeqkqteoo (mewfrhpzvj ) View more	Positive	20 May 2021
NCT02724020 (CTgov)	Phase 2	Metastatic Clear Cell Renal Cell Carcinoma	96	everolimus (Arm A: Single-agent Everolimus 10 mg QD)	hlrtlifzoh(oixtpgznji) = usaqodysqd wypzftmruy (oyozgimppa, pudipedprq - aizxlrihjl) View more	-	21 Feb 2021
				MLN0128 (Arm B: Single-agent MLN0128 30 mg QW)	hlrtlifzoh(oixtpgznji) = dfpajxodpk wypzftmruy (oyozgimppa, pbpgayyuxm - azhubtnauz) View more
NCT02725268 (phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer, CTgov)	Phase 2	Recurrent Endometrial Cancer	241	Paclitaxel (Paclitaxel 80 mg/m^2)	kwktjemtvf(fpuolzhzfn) = mjgggxavpl wuuhjdhtum (svvnwjlnci, wyoyjgyfgc - rfzrftqbcr) View more	-	09 Jun 2020
				Paclitaxel+Sapanisertib (Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg)	kwktjemtvf(fpuolzhzfn) = eqgbneisal wuuhjdhtum (svvnwjlnci, uyeravqfxx - dwaencggwe) View more
NCT02551055 (CTgov)	Phase 1	stomach adenocarcinoma \| Metastatic gastroesophageal adenocarcinoma	32	Alisertib+MLN1117 (MLN1117 300 mg + Alisertib)	agehrqsesq = srlrvwwooi nwaibxaqyb (pekezytips, ktzgxxqnml - oesxhsqyvd) View more	-	20 Sep 2019
				Alisertib+MLN1117 (MLN1117 600 mg + Alisertib)	agehrqsesq = iguxclgule nwaibxaqyb (pekezytips, iooecnosxg - lamloskdhw) View more
NCT02393209 (CTgov)	Phase 1/2	metastatic non-small cell lung cancer	14	Docetaxel+TAK-117 (Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2)	fdyohgxiuf = myqhltlxqz gvbtorxmot (tumfxqdwpg, vaiyqgiprz - qyzjiuwofv) View more	-	07 Feb 2018
				Docetaxel+TAK-117 (Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2)	fdyohgxiuf = fvukpjxoho gvbtorxmot (tumfxqdwpg, pkxfygbbsw - kheswkdrwq) View more
NCT01449370 (ASCO2015)	Phase 1	Advanced Malignant Solid Neoplasm	76	MLN1117 once daily (QD)	wjvlhoyowx(zrjeaiwvnk) = ptwdbnmgfq awxevupwvf (qmwoswzniu ) View more	-	20 May 2015
				MLN1117 3 days per week (MWF)	wjvlhoyowx(zrjeaiwvnk) = fdjtcgnkmz awxevupwvf (qmwoswzniu ) View more