In vitro experiments confirmed that vincristine successfully inhibited U87 cell proliferation and induced G1 phase arrest via the PI3K/AKT signaling pathway, thereby reducing cell growth. The study results indicate that the PI3K/AKT signaling pathway may be involved in the mechanism by which vincristine inhibits the proliferation of glioma cells.

SS exerted its anti-cervical cancer effects by inhibiting cell proliferation, promoting apoptosis, and inhibiting the PI3K/AKT signaling pathway.

Furthermore, PFBA up-regulated the proliferation-related factors downstream of ERRγ and inhibited by PI3K/Akt inhibitor LY294002, which also suppressed the cell proliferation induced by PFBA. Taken together, the results revealed that PFBA had estrogen effects at the human-related exposure concentration, and demonstrated a new estrogen effects mechanism of PFBA via ERRγ pathway.

P2, N=63, Not yet recruiting, Peking University

P2, N=14, Recruiting, MedSIR | N=28 --> 14

P1, N=9, Terminated, Taipei Medical University Shuang Ho Hospital | Trial completion date: Dec 2024 --> Mar 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Mar 2024; The overall profile does not support development for metastatic colorectal cancer

PI3K inhibitor LY294002 intervention could reduce the promoting effect of AU on ribosome biogenesis. The above results suggest that AU can improve the injury of nucleus pulposus cells and ECM degradation, and its mechanism of action is related to its activation of the PI3K/mTOR pathway to promote ribosome biogenesis.

R. roxburghii polysaccharides may inhibit the proliferation of DU145 cells and induce its apoptosis by inhibiting the PI3K/Akt/mTOR pathway and clearing intracellular ROS.

Taken together, the current work emphasizes the potential effects of Daidzein from Phoenix dactylifera L. against TNBC, and it can be further studied to establish it as a standard chemotherapy for TNBC.

e-Pharmacophore model was generated using Receptor-Ligand complex using the Inavolisib drug (PDB:8EXV) and phase screening was performed using the Molport database of natural compounds...These compounds demonstrated favorable results in several parameters, including RMSD, RMSF, Rg, SASA, PCA, FEL, and total energy evaluations. Therefore, these compounds are projected to function as PI3K-α inhibitors and because of its natural origin it can possess fewer side effects than the conventional medicine, which should be validated by proper in vivo and in vitro models.

P3, N=701, Recruiting, Celcuity Inc | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2024 --> Mar 2025

P3, N=252, Terminated, Incyte Corporation | Active, not recruiting --> Terminated; The study was terminated due to futility.

Additionally, we found that PIK-75 oc-HDL NP, but not free PIK-75 or oc-HDL NP alone, reduced the IC50 in the NCI-60 cell line panel and additional pancreatic cancer cell lines. These data demonstrate the first example of drug-loaded oc-HDL NP that actively target SR-B1 and kill cancer cells in vitro and in vivo, encouraging further development and translation to human patients.

Besides BAY-293, BH1406 cells proved to be sensitive to the SOS1 inhibitors MRTX0902 and BI-3406...Additionally, the PI3K inhibitor dactolisib, the GSK-3 inhibitor BI-5521 as well as the bromodomain protein-directed PROTAC ARV-771 inhibited the growth of BH1406 cells significantly and showed synergistic interaction with BAY-293...BH1406 cells represent a novel cellular model suitable for the molecular characterization of SOS1 druggability. Such rare oncogenic driver genes are not included in standard NGS panels and need to be detected by expanded assays like WES.

Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

P2, N=20, Recruiting, Shanghai Jiatan Pharmatech Co., Ltd | Trial completion date: Dec 2025 --> Dec 2026

P1/2, N=108, Active, not recruiting, Suzhou Junde Biotechnology Co., Ltd | Not yet recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jun 2025 | Trial primary completion date: Jan 2024 --> Nov 2024

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 .

These findings support the potential of rNDV-PTEN as a safe and effective therapy for PDAC with highly activated PI3K/AKT/mTOR signaling caused by KRAS and PTEN gene mutations. Thus, PTEN gene-containing rNDV may be a promising candidate for pancreatic cancer treatment.

P3, N=423, Active, not recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Mar 2025 --> Jun 2025

P2, N=45, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial completion date: Sep 2023 --> Oct 2025 | Trial primary completion date: Sep 2022 --> Aug 2024

P3, N=430, Recruiting, Chipscreen Biosciences, Ltd. | Not yet recruiting --> Recruiting

These findings demonstrate that amdizalisib is rapidly absorbed, extensively metabolized, and primarily excreted via feces and urine, supporting its continued development as a potential therapeutic for Hodgkin's lymphoma. https://www.chinadrugtrials.org.cn/, identifier CTR20212448.

Our findings provide a novel mechanism by which TRPV4 directly activates Ca2+/FAK/PI3K/AKT/GSK3β pathway and further indirectly enhances the FAK/PI3K/AKT/GSK3β pathway through the promotion and secretion of ECM1 to promote LMS malignant progression. Targeting the TRPV4/FAK axis might be a promising potential strategy for prognosis and treatment of LMS.

The detailed molecular mechanisms were subsequently elucidated, and it was found that miR-155-5p bound with HuR to increase the stability and expression levels of VEGFR2, which further activated the tumor-promoting PI3K/Akt/mTOR signal pathway, and M2-exos-enhanced cancer progression in NSCLC cells were apparently suppressed by downregulating VEGFR2 and PI3K inhibitor LY294002 co-treatment. Taken together, M2-polarized TAMs secreted miR-155-5p-containing exosomes to enhanced cancer aggressiveness of NSCLC by activating the VEGFR2/PI3K/Akt/mTOR pathway in a HuR-dependent manner.

P2, N=100, Recruiting, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

In our study, the in vitro and in vivo experiments confirmed that chidamide and venetoclax synergistically inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of HDAC and BCL2, inhibiting the Wnt/β-catenin signaling pathway and B-ALL cell proliferation. These findings indicate that the HDACi chidamide and the BCL2 inhibitor venetoclax can be used in combination to treat B-ALL, providing a new method and strategy for treating B-ALL.

LY294002 further alleviated BCP in rats, while the effects were reversed after treatment with insulin-like growth factor 1 (IGF-1). Both LSW and its active ingredient Bufalin were shown to inhibit the viability and migration of Walker 256 cells and induce apoptosis. Bufalin appears to be the key active ingredient of LSW and exerts its pain-relieving effects by suppressing PI3K/Akt and TRPV1 signaling in BCP.

We screened PI-103 as the most promising candidate for patients with higher CupScore and confirmed its experimental evidence and clinical trial status...Cuproptosis has the ability to reprogram the tumor microenvironment (TME) in HGG, leading to the stratification of patients into two distinct molecular subgroups. The CupScore model emerged as a robust metric for predicting the prognostic and therapeutic benefits, as well as may therefore facilitate personalized treatment strategies for patients with HGG.

In addition, luteolin downregulated the expression of p-Akt (Ser473), MDM2, and Bcl-2 but upregulated the expression of p53 and Bax, which was consistent with the effect of LY294002. Luteolin had a good anti-NSCLC effect, and the apoptosis-inducing effect might be related to the Akt/MDM2/p53 signaling pathway.

P1/2, N=100, Recruiting, Shanghai Jiatan Pharmatech Co., Ltd | Trial completion date: Mar 2025 --> Nov 2025 | Trial primary completion date: Mar 2025 --> Nov 2025

LY294002 blocked SYK (L) knockdown-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas IGF-1 rescued the decreased migration, invasion and EMT induced by SYK (S) knockdown. The results suggest that SYK(L) and SYK(S) are involved in the progression of cervical cancer through PI3K/AKT signaling pathway, and may serve as potential targets for clinical treatment of advanced cervical cancer.

Imiquimod (IMQ)-induced psoriasis-like mice were used to verify the therapeutic effects of SCP...Besides, SCP could also inhibit the phosphorylation of PI3K, Akt, and mTOR, and the good docking activity of SCP with the three pathway proteins further proved SCP can treat psoriasis via PI3K/Akt/mTOR signaling pathway. In conclusion, SCP may be a potential drug for treating psoriasis and is worth further research.

P2, N=49, Recruiting, Ruijin Hospital

P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=70, Recruiting, Shanghai Jiatan Pharmatech Co., Ltd | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

Chaperonin TCP1 subunit 6A (CCT6A) plays an oncogenic role in triple-negative breast cancer (TNBC) through the AKT signaling pathway. TRIM21 facilitated K48-linked ubiquitination-mediated degradation of CCT6A, thereby impeding TNBC progression. Our study collectively underscores the potential of Ipatasertib in conjunction with anti-PD1 therapy as a promising strategy to counteract CCT6A/AKT hyperactivity-driven TNBC progression.

The evaluation results show that our model achieves the highest average AUC-ROC and AUC-PR values on the test set, which are 0.927 ± 0.006 and 0.980 ± 0.002, respectively. This study provides a reference for exploring the structure-activity relationship of PI3K inhibitors.

P1/2, N=54, Completed, Incyte Corporation | Active, not recruiting --> Completed

P2, N=44, Recruiting, Zhejiang Cancer Hospital | Not yet recruiting --> Recruiting

This was accompanied by reduced expression of AKT1 and ABCB1 genes, reinforcing the anticancer efficacy of PD/SOF combination therapy. In conclusion, the findings suggest that PD/SOF could serve as a promising anticancer treatment strategy, warranting further investigation for potential clinical applications and mechanistic studies in vivo.

Linperlisib showed an acceptable safety profile and preliminary clinical benefit in patients with a range of advanced solid tumors. Further studies of linperlisib safety and efficacy are warranted.