Akt inhibitors(Proto-oncogene proteins c-akt inhibitors), PI3Kγ inhibitors(Phosphatidylinositol 3 kinase gamma inhibitors), mTOR inhibitors(Serine/threonine-protein kinase mTOR inhibitors)

Therapeutic Areas

NeoplasmsNervous System Diseases

Active Indication

Solid tumorDementia

Inactive Indication-

Originator Organization

Thryv Therapeutics, Inc.Startup

Active Organization

Amylyx Pharmaceuticals, Inc.

University Hospital Heidelberg

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with AKT/PI3K/mTOR inhibitors(Thryv Therapeutics)

100 Translational Medicine associated with AKT/PI3K/mTOR inhibitors(Thryv Therapeutics)

100 Patents (Medical) associated with AKT/PI3K/mTOR inhibitors(Thryv Therapeutics)

Literatures (Medical) associated with AKT/PI3K/mTOR inhibitors(Thryv Therapeutics)

01 Jan 2025·Journal of Affective Disorders

Electroconvulsive therapy combined with esketamine improved depression through PI3K/AKT/GLT-1 pathway

Article

Author: Hu, Jingping ; Zhang, Jingting ; Zang, Xiangyang ; Mo, Xingying ; Zhou, Shaoli ; Chen, Chaojin ; Zheng, Tingwei ; Ji, Jiaming ; Xing, Jibin

Neuron excitotoxic damage induced by extracellular glutamate accumulation pathologically is one of the main mechanisms of depression. Glutamate transporter-1 (GLT-1) expressed in astrocyte is responsible for glutamate clearance to maintain glutamate balance. Electroconvulsive therapy (ECT) is prevalently recommended for severe depression due to its significant anti-depressant effect. Esketamine could offer advantages of rapid anti-depressant effect and neuron protection. The aim of this study is to investigate the anti-depressant efficacy of esketamine plus ECT, and further to explore the mechanism. Firstly, total 12 patients were randomized into anesthesia with propofol (P) or propofol+esketamine (PK) before ECT. 24-Hamilton Depression Scale (HAMD) was used to evaluate the severity of depression after each ECT. Then, depressive rat model was built using chronic unpredictable mild stress method, and subsequently received infusion of esketamine (5 mg/kg) or saline before ECT treatment (0.5 mA; 100 V) for consecutive 10 days. Tests including sucrose preference test, open field test and forced swimming test were used to evaluate depression-like behaviors. In next experiments, rats were injected with RIL, DHK or LY294002 intracerebroventricularly for continuous 10 days before individual treatment. After the fifth and sixth ECT, PK group displayed lower HAMD score compared to P group. In rat model, we found that esketamine plus ECT could significantly improve depression-like behaviors and decrease glutamate level. Esketamine and ECT could both activate PI3K/Akt/GLT-1 pathway. The GLT-1 agonist RIL made equivalent effect as esketamine plus ECT. Furthermore, after using PI3K/Akt inhibitor LY294002 and GLT-1 inhibitor DHK, esketamine plus ECT could neither improve depression-like symptoms, nor upregulate GLT-1 level. Our present study suggested that esketamine plus ECT could dramatically improve depression symptom. The activation of PI3K/Akt/GLT-1 pathway may be the potential mechanism.

01 Oct 2022·European review for medical and pharmacological sciences

Efficacy and safety of PI3K/Akt/mTOR inhibitors combined with trastuzumab therapy for HER2-positive breast cancer: a meta-analysis.

Article

Author: Zhu, X-Z ; Huang, B-Q ; Peng, D-S ; Ning, H T

OBJECTIVEActivation of the PI3K/AKT/mTOR pathway in patients with HER2-positive breast cancer is associated with acquired resistance to trastuzumab. This randomized controlled trial (RCTs) meta-analysis was designed to evaluate the clinical efficacy and safety of PI3K/Akt/mTOR inhibitors in combination with trastuzumab in HER2-positive breast cancer.MATERIALS AND METHODSWe searched on Web of Knowledge, PubMed, Embase, Cochrane, CNKI, and ClinicalTrials.Gov for RCTs comparing PI3K/Akt/mTOR inhibitors plus trastuzumab vs. standard trastuzumab treatments. Pooled estimates of progression-free survival (PFS), pathologic complete response (pCR), and incidence of adverse events were determined.RESULTS5 studies out of 610 were found to be eligible and were included in our analysis (n=1,548 participants). PI3K/Akt/mTOR inhibitors combination with trastuzumab treatments resulted in a statistically significant increase in PFS compared with conventional trastuzumab therapy (HR 0.82; 95% CI: 0.76-0.90; p<0.00001). The new combination treatment was more effective on hormone receptor-negative patients (HR 0.73; 95% CI: 0.58-0.93; p=0.010). In addition, the combination of PI3K/Akt/mTOR inhibitors with trastuzumab slightly increased the risk of some adverse events, such as neutropenia, leukopenia, fatigue, and anemia.CONCLUSIONSThe combination treatments of PI3K/Akt/mTOR inhibitors and trastuzumab for PI3K/Akt/mTOR inhibitors combined with trastuzumab treatments for patients with HER2-positive breast cancer can improve median progression-free survival while increasing the incidence of adverse events. It is still controversial based on the current evidence. Due to the limited number and quality of included studies, more high-quality studies are needed for further analysis.

01 Oct 2022·Seminars in Cancer BiologyQ1 · MEDICINE

Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer

Q1 · MEDICINE

Review

Author: Wei, Jessica ; Liu, Pengda ; Yu, Le

Cancer is the second leading cause of human death globally. PI3K/Akt/mTOR signaling is one of the most frequently dysregulated signaling pathways observed in cancer patients that plays crucial roles in promoting tumor initiation, progression and therapy responses. This is largely due to that PI3K/Akt/mTOR signaling is indispensable for many cellular biological processes, including cell growth, metastasis, survival, metabolism, and others. As such, small molecule inhibitors targeting major kinase components of the PI3K/Akt/mTOR signaling pathway have drawn extensive attention and been developed and evaluated in preclinical models and clinical trials. Targeting a single kinase component within this signaling usually causes growth arrest rather than apoptosis associated with toxicity-induced adverse effects in patients. Combination therapies including PI3K/Akt/mTOR inhibitors show improved patient response and clinical outcome, albeit developed resistance has been reported. In this review, we focus on revealing the mechanisms leading to the hyperactivation of PI3K/Akt/mTOR signaling in cancer and summarizing efforts for developing PI3K/Akt/mTOR inhibitors as either mono-therapy or combination therapy in different cancer settings. We hope that this review will facilitate further understanding of the regulatory mechanisms governing dysregulation of PI3K/Akt/mTOR oncogenic signaling in cancer and provide insights into possible future directions for targeted therapeutic regimen for cancer treatment, by developing new agents, drug delivery systems, or combination regimen to target the PI3K/Akt/mTOR signaling pathway. This information will also provide effective patient stratification strategy to improve the patient response and clinical outcome for cancer patients with deregulated PI3K/Akt/mTOR signaling.

100 Deals associated with AKT/PI3K/mTOR inhibitors(Thryv Therapeutics)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Preclinical	-	University Hospital Heidelberg	14 Dec 2022
Dementia	Preclinical	-	Amylyx Pharmaceuticals, Inc.	29 Nov 2022

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AKT/PI3K/mTOR inhibitors(Thryv Therapeutics)

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