The goal of this clinical trial is to learn about treatment for a type of brain tumor called a meningioma. This study will enroll two groups of people. One group will be for people who will receive surgery to remove their brain tumor. The other group will be for people who have previously received treatment for their brain tumor but do not have any other available options for treatment.
The primary goals of this study are:
1. To measure how much of the study drug is present in tumor tissue taken from patients during surgery to remove their brain tumor
2. To measure the length of time between a study participant's first dose of study treatment until the time when their brain tumor gets worse or their death

Start Date01 Nov 2024

Sponsor / Collaborator

University of Nebraska

[+1]

NCT06613516 / Not yet recruitingPhase 2IIT

CaptAin - Effect of Capivasertib on ctDNA in ER Positive Breast Cancer

There is growing evidence that cancer DNA (called circulating tumour DNA - ctDNA) in the blood is often an early sign that the cancer is likely to return. The aim of this study is to investigate whether treating women who have detectable ctDNA in their blood with a drug called Capivasertib can help control ctDNA levels and prevent developing metastatic or secondary breast cancer.
A recruitment of 20 women with oestrogen receptor (ER) positive breast cancer (who are already on standard of care hormone therapy who are being treated with curative intent) is aimed for; which means that the disease has not yet spread to distant parts of the body. Each subject will be dosed with 400mg of Capivasertib twice a day for a maximum period of two years.

Start Date01 Nov 2024

Sponsor / Collaborator

Imperial College London

[+3]

NCT05630794 / Not yet recruitingPhase 1IIT

Phase 1 Trial of ONC201 for Chemoprevention of Colorectal Cancer

This phase I trial tests the safety, side effects, and best dose of Akt/ERK Inhibitor ONC201 (ONC201) in preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) or a history of multiple polyps. ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date08 Oct 2024

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Akt-1

100 Translational Medicine associated with Akt-1

0 Patents (Medical) associated with Akt-1

21,348

Literatures (Medical) associated with Akt-1

01 Dec 2025·CURRENT ALLERGY AND ASTHMA REPORTS

Mechanisms of Bone Morphogenetic Protein 2 in Respiratory Diseases

Review

Author: Wen, Yiqiong ; Lu, Qiongfen ; Sun, Shibo ; Li, Min ; Li, Tongfen ; Zheng, Yuanyuan ; Bi, Xiaoqing ; Hua, Shu

PURPOSE OF REVIEW:

Bone morphogenetic protein 2 (BMP2) belongs to the transforming growth factor-β (TGF-β) superfamily and plays an important role in regulating embryonic development, angiogenesis, osteogenic differentiation, tissue homeostasis, and cancer invasion. Increasing studies suggest BMP2 is involved in several respiratory diseases. This study aimed to review the role and mechanisms of BMP2 in respiratory diseases.

RECENT FINDINGS:

BMP2 signaling pathway includes the canonical and non-canonical signaling pathway. The canonical signaling pathway is the BMP2-SMAD pathway, and the non-canonical signaling pathway includes mitogen-activated protein kinase (MAPK) pathway and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. The BMP2 is related to pulmonary hypertension (PH), lung cancer, pulmonary fibrosis (PF), asthma, and chronic obstructive pulmonary disease (COPD). BMP2 inhibits the proliferation of pulmonary artery smooth muscle cells (PASMCs), promotes the apoptosis of PASMCs to reduce pulmonary vascular remodeling in PH, which is closely related to the canonical and non-canonical pathway. In addition, BMP2 stimulates the proliferation and migration of cells to promote the occurrence, colonization, and metastasis of lung cancer through the canonical and the non-canonical pathway. Meanwhile, BMP2 exert anti-fibrotic function in PF through canonical signaling pathway. Moreover, BMP2 inhibits airway inflammation to maintain airway homeostasis in asthma. However, the signaling pathways involved in asthma are poorly understood. BMP2 inhibits the expression of ciliary protein and promotes squamous metaplasia of airway epithelial cells to accelerate the development of COPD. In conclusion, BMP2 may be a therapeutic target for several respiratory diseases.

01 Apr 2025·Neural Regeneration Research

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Article

Author: Leyton, Lisette ; Pérez-Núñez, Ramón ; González, María Fernanda ; Avalos, Ana María

Astrocytes are the most abundant type of glial cell in the central nervous system. Upon injury and inflammation, astrocytes become reactive and undergo morphological and functional changes. Depending on their phenotypic classification as A1 or A2, reactive astrocytes contribute to both neurotoxic and neuroprotective responses, respectively. However, this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries. Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles, which emphasizes the heterogeneous nature of their reactivity. Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types, releasing cytokines, and influencing the immune response. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior, as evidenced by in silico, in vitro, and in vivo results. In astrocytes, inflammatory cues trigger a cascade of molecular events, where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses. Here, we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation. We highlight the involvement of various signaling pathways that regulate astrocyte reactivity, including the PI3K/AKT/mammalian target of rapamycin (mTOR), αvβ3 integrin/PI3K/AKT/connexin 43, and Notch/PI3K/AKT pathways. While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage, evidence suggests that activating this pathway could also yield beneficial outcomes. This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation. The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior. The findings should then be validated using in vivo models to ensure real-life relevance. The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage, although further studies are required to fully comprehend its role due to varying factors such as different cell types, astrocyte responses to inflammation, and disease contexts. Specific strategies are clearly necessary to address these variables effectively.

01 Feb 2025·Current Computer-Aided Drug Design

Prescription Data Mining and Network Pharmacology Study of 1152 Patients with Rectal Prolapse using Traditional Chinese Medicine

Article

Author: Tang, Shao-liang ; Gong, Yue ; Zhang, Meng ; Yang, Tong-ling ; Cheng, Yan

Background::

In recent years, the incidence of rectal prolapse has increased significantly due to the sedentary lifestyle and irregular eating habits of modern life. However, there is a lack of clinical studies on the treatment of rectal prolapse with traditional Chinese medicine (TCM) with a large sample size. Therefore, this study investigated the characteristics of rectal prolapse treatment formulas and then studied the network pharmacology of their core therapeutic drugs, which can help to provide a reference for the treatment and postoperative care of rectal prolapse patients.

Objective::

This study aimed to explore the prescription characteristics and the mechanism of action of core drugs in the treatment of rectal prolapse in Chinese medicine through data mining and bioinformatics techniques.

Methods::

We collected the diagnosis and treatment information of patients with rectal prolapse from January 2014 to September 2021 in the electronic case database of Nanjing Hospital of TCM, mined the patient information and prescription features using R, screened the active ingredients of the core pairs of drugs and disease drug intersection targets using TCMSP and GnenCard databases, and constructed a Protein-protein interaction (PPI) network using STRING and Cytoscape, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the intersecting targets were performed using Metascape and R.

Results::

We found that prolapse is easy to occur in people over 50 years old, preferably in autumn and winter. Commonly used therapeutic Chinese medicines include Glycyrrhiza glabra, Radix angelicae sinensis, Radix astragali, Atractylodes macrocephala, and Pericarpium citri reticulatae, which are mostly deficiency tonic medicines, warm in nature, and belong to spleen meridian. The core therapeutic medicinal pair was “Bupleuri radix-Cimicifugae rhizoma”. There were 190 common targets of Bupleuri radix and Cimicifugae rhizoma, and 71 intersection targets of the drug pair and prolapse. The main components of the core drugs for the treatment of prolapse may be quercetin, kaempferol, Stigmasterol, etc, and the core targets may be CASP3, AKT1, HIF1A, etc. The total number of GO entries for the intersection targets of “Bupleuri radix-Cimicifugae rhizoma” and diseases was 3495, among which the molecular functions accounted for the largest proportion, mainly Pathways in cancer, IL-18 signaling pathway, etc. KEGG enriched pathway analysis yielded 168 results, and the major pathways were pathways in cancer, lipid and atherosclerosis, IL-17 signaling pathway, etc.

Conclusion::

This study adopted real-world research methodology and used data mining and bioinformatics technology to mine the medication law of rectal prolapse and its core drug action mechanism from the clinical information of Chinese medicine.

176

News (Medical) associated with Akt-1

31 Oct 2024

·pipelinereview.com

Alterome Therapeutics Announces First Patient Dosed in Phase 1 Study of ALTA2618 in AKT1 E17K-mutant solid tumors (AKTive-001)

AKTive-001 is a Phase 1/1b study of ALTA2618 in adults with AKT1 E17K-mutant solid tumors ALTA2618 is the first clinical mutant-selective inhibitor of AKT SAN DIEGO, CA, USA I October 30, 2024 I Alterome Therapeutics, Inc. , a clinical stage biopharmaceutical company pioneering the development of next generation, small molecule targeted therapies for the treatment of cancer, today announced the dosing of the first patient in AKTive-001, a Phase 1/1b trial of ALTA2618 in adults with AKT1 E17K-mutant advanced solid tumors. ALTA2618 is the first mutant-selective allosteric inhibitor of AKT1 E17K and is designed to avoid on-target toxicities associated with inhibition of AKT family kinases. AKT1 E17K is a clinically validated oncogene that drives ~5% of breast cancer, particularly hormone positive disease, and 1-2% of all cancer, including endometrial (~3%) and prostate (~2%) cancers. “Dosing the first patient in the AKTive-001 trial marks a significant milestone for Alterome as we advance the first program from our mutation-selective and isoform-selective discovery pipeline to the clinic,” said Eric Murphy, Ph.D., co-founder and CEO of Alterome Therapeutics. “ALTA2618 was designed to selectively target the AKT1 E17K mutation by pioneering a novel covalent approach to capture the lysine mutation. From concept to clinic, ALTA2618 illustrates the relentless execution of our team and dedication to developing novel mutation-selective therapies that will improve outcomes for patients with cancer.” AKTive-001 is a Phase 1/1b, open-label, dose escalation and multiple expansion cohort study evaluating ALTA2618 as an oral monotherapy. The study will evaluate the safety, tolerability, pharmacokinetics, and preliminary clinical activity of ALTA2618 in patients aged 18 years or above with AKT1 E17K-mutated advanced unresectable or metastatic solid tumors (NCT06533059). Additional clinical sites across Europe, Asia and Australia will initiate enrollment over the next year. About Alterome Therapeutics, Inc. Alterome Therapeutics, Inc. is a precision oncology biotech developing alteration-specific therapeutics to address high-value and validated oncogenic drivers. The company is led by an expert team of precision oncology R&D leaders with a history of developing marketed oncology small molecule drugs. For more information, visit www.alterome.com . Follow us on LinkedIn and Twitter . SOURCE: Alterome Therapeutic

Phase 1

23 Oct 2024

·pipelinereview.com

Atavistik Bio Presents Preclinical Data on Precision Oncology Development Candidate, ATV-1601, a Selective Allosteric AKT1 E17K Small Molecule Inhibitor, at EORTC-NCI-AACR Symposium

CAMBRIDGE, MA, USA I October 23, 2024 I Atavistik Bio, a biotechnology company discovering the next generation of precision allosteric therapeutics inspired by the body’s natural regulators, today presented preclinical data at the 36 th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics Meeting 2024 in Barcelona for ATV-1601, the company’s orally bioavailable selective allosteric small molecule inhibitor for AKT1 E17K-driven cancers. The preclinical data demonstrated that as a selective allosteric AKT1 E17K inhibitor, ATV-1601 provides enhanced target inhibition, superior efficacy and improved tolerability compared to pan-AKT inhibitors in preclinical models. Atavistik Bio anticipates initiating a first-in-human study with ATV-1601 in patients with AKT1 E17K mutant tumors in early 2025. AKT1 E17K is a clinically validated oncogene that impacts greater than 40,000 cancer patients per year in the United States, with the highest prevalence in breast, endometrial, and prostate cancers. In addition, early evidence indicates that the AKT1 E17K mutation appears to be an emerging mechanism of resistance to PI3Kα-targeted cancer therapies. The only approved AKT-targeted therapy is a pan-AKT inhibitor that blocks all three isoforms of AKT (AKT1, AKT2, and AKT3). Pan-AKT inhibitors offer limited efficacy for patients with AKT1 E17K-driven mutant tumors due to insufficient inhibition of the AKT1 E17K mutation. Additionally, pan-AKT inhibitors can cause significant adverse events, such as AKT2-driven hyperglycemia, rash, and diarrhea, which lead to treatment discontinuation or dose reductions in a considerable subset of patients. Data presented in today’s poster entitled, “ATV-1601 is a Potent and Selective Allosteric Inhibitor of AKT1 E17K and Shows Profound and Durable Regressions in AKT1 E17K-Driven Patient-Derived Xenograft Models,” demonstrates that the selectivity profile of ATV-1601 enables greater than 90% target engagement without inducing hyperglycemia in preclinical models. As a result of this potent target engagement and selectivity, ATV-1601 demonstrated profound and durable tumor regression in multiple AKT1 E17K driven patient-derived breast and endometrial tumor models and was well tolerated. “We are pleased to share these exciting preclinical data for our ATV-1601 program with the oncology community,” said Marion Dorsch, Ph.D., President and Chief Scientific Officer, Atavistik Bio. “As a selective allosteric AKT1 E17K inhibitor, ATV-1601 has the potential to be a transformative precision therapy against the validated AKT1 E17K oncogenic driver. The patient populations impacted by the AKT1 E17K mutation have a significant unmet need, which we are working with urgency to address. We look forward to transitioning into the clinic in our planned first-in-human study.” About Atavistik Bio Atavistik Bio is a biotechnology company accelerating the discovery and development of transformative precision allosteric therapeutics to address serious unmet patient needs, with a focus on oncology. Atavistik Bio is led by an experienced team of drug hunters with a proven track record of developing marketed small molecule therapies and supported by top-tier investors, including The Column Group, Nextech Invest, and Lux Capital. To learn more, visit us at atavistikbio.com and follow us on LinkedIn . SOURCE: Atavistik Bio

AACR

15 Oct 2024

·www.globenewswire.com

Atavistik Bio Announces Nomination of Precision Oncology Development Candidate, ATV-1601, a Selective Allosteric AKT1 E17K Small Molecule Inhibitor

AKT1 E17K mutation is a clinically validated oncogene that impacts greater than 40,000 cancer patients per year in the United States, with the highest prevalence in breast, endometrial, and prostate cancersAs a selective allosteric AKT1 E17K inhibitor, ATV-1601 has the potential to provide enhanced target inhibition, superior efficacy and improved tolerability compared to pan-AKT inhibitorsAtavistik Bio anticipates initiating a first-in-human study with ATV-1601 in patients with AKT1 E17K mutant tumors in early 2025Preclinical data on ATV-1601 to be presented at the EORTC-NCI-AACR Symposium on October 23, 2024The company continues to leverage the AMPS™ platform to bring forward additional high-value precision oncology programs CAMBRIDGE, Mass., Oct. 15, 2024 (GLOBE NEWSWIRE) -- Atavistik Bio, a biotechnology company discovering the next generation of precision allosteric therapeutics inspired by the body’s natural regulators, today announced its precision oncology development candidate ATV-1601, an orally bioavailable selective allosteric small molecule inhibitor for AKT1 E17K-driven cancers. ATV-1601 was developed leveraging the company’s AMPS™ technology, which is seamlessly integrated with its AI-enabled drug discovery engine to rapidly advance programs from discovery into development. “ATV-1601’s nomination as our first oncology development candidate is a major milestone for the company, validating the capabilities of our proprietary platform to rapidly discover and advance novel precision allosteric therapeutics for targets that have historically been hard to drug. We anticipate significant progress in our portfolio in the upcoming year for high value oncology targets that address the unmet needs of large patient populations,” said Bryan Stuart, Chief Executive Officer, Atavistik Bio. “We are working to quickly advance ATV-1601 to the clinic and to achieve early clinical proof of concept for this program. We believe our precision allosteric small molecule offers several advantages to target the difficult-to-drug AKT1 E17K mutation, with the potential to improve the lives of many cancer patients.” AKT1 E17K mutation is a clinically validated oncogene that impacts greater than 40,000 cancer patients per year in the United States, with the highest prevalence in breast, endometrial, and prostate cancers. In addition, early evidence indicates that the AKT1 E17K mutation appears to be an emerging mechanism of resistance to PI3Kα-targeted cancer therapies. A selective allosteric AKT1 E17K inhibitor has the potential to be a transformative therapy against the validated AKT1 E17K oncogenic driver as well as resistance mutations emerging from PI3Kα-targeted therapies. The only approved AKT-targeted therapy is a pan-AKT inhibitor that blocks all three isoforms of AKT (AKT1, AKT2, and AKT3). Pan-AKT inhibitors offer limited efficacy for patients with AKT1 E17K-driven mutant tumors due to insufficient inhibition of the AKT1 E17K mutation. Additionally, pan-AKT inhibitors can cause significant adverse events, such as AKT2-driven hyperglycemia, rash, and diarrhea, which leads to treatment discontinuation or dose-reductions in a considerable subset of patients. ATV-1601, a selective allosteric AKT1 E17K inhibitor, has the potential to provide enhanced target inhibition, superior efficacy and improved tolerability compared to pan-AKT inhibitors for AKT1 E17K-driven cancers. Atavistik Bio anticipates initiating a first-in-human study with ATV-1601 in patients with AKT1 E17K-mutant tumors in early 2025. “Behind ATV-1601, we have a robust pipeline of precision oncology programs derived from our AMPS platform, said Marion Dorsch, Ph.D., President and Chief Scientific Officer, Atavistik Bio. “We look forward to advancing our internal pipeline with urgency while also broadening the reach of our platform through partnerships to discover important new allosteric therapeutics across other diseases.” Atavistik Bio EORTC-NCI-AACR Symposium Data Presentation Details Date:Wed., October 23, 2024Time:12.00 – 19.00 CETPoster Session:New DrugsPoster Title:ATV-1601 is a Potent and Selective Allosteric Inhibitor of AKT1 E17K and Shows Profound and Durable Regressions in AKT1 E17K-Driven Patient-Derived Xenograft ModelsPoster #:PB128 About Atavistik Bio Atavistik Bio is a biotechnology company accelerating the discovery and development of transformative precision allosteric therapeutics to address serious unmet patient needs, with a focus on oncology. Atavistik Bio is led by an experienced team of drug hunters with a proven track record of developing marketed small molecule therapies and supported by top-tier investors, including The Column Group, Nextech Invest, and Lux Capital. To learn more, visit us at atavistikbio.com and follow us on LinkedIn. Media Contact: Liz MeloneMelone Communications, LLCliz@melonecomm.com

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