buparlisib (AN2025)

Comparative docking with five reference drugs (Alpelisib, Buparlisib, Lapatinib, Gefitinib, and Afatinib) identified nine flavonoids; Sphaerobioside, Avicularin, Nicotiflorin, Myricetin, Quercitrin, Rutin, Isoquercetin, Didymin, and Robinin as promising candidates with favorable binding affinities and stable receptor interactions...Collectively, these findings highlight the multitarget inhibitory potential of selected flavonoids and demonstrate how integrated computational profiling can accelerate the discovery and optimization of natural product-based anticancer agents. The online version contains supplementary material available at 10.1007/s40203-025-00489-0.

P3, N=487, Completed, Adlai Nortye Biopharma Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Nov 2025 | Trial primary completion date: Jun 2025 --> Nov 2025

Vitamin D represents an efficient anticancer adjuvant that permits a novel therapeutic strategy for cancer patients.

Two lead compounds, Anonaine (CID_160597) and Dehydroaporheine (CID_161899), exhibited more binding abilities towards the PI3Kα protein than the reference inhibitor buparlisib...This research lays the groundwork for additional experimental confirmation and underscores the promise of N. nucifera products in creating effective alternative therapies against breast cancer. This research may contribute to advancing personalised medicine approaches in oncology, offering new avenues for targeted therapies in PIK3CA-mutant breast cancer.

The interleukin (IL)-33/thymic stromal lymphopoietin (TSLP)/IL-7-induced growth of group 2 innate lymphoid cells (ILC2) in vitro was resistant to dexamethasone (DEX), but suppressed by everolimus, an mTOR inhibitor, in a concentration-dependent manner...The combination of the pan-class I phosphatidylinositide-3 kinase inhibitor, buparlisib and the pan-Akt inhibitor, capivasertib also attenuated the resistance of IL-33/TSLP/IL-7-exposed ILC2s to DEX...This study demonstrates that activation of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (mTOR) pathway induces steroid resistance in group 2 innate lymphoid cells. Targeting mTOR with everolimus restores steroid sensitivity, highlighting mTOR inhibition as a promising pharmacotherapy for steroid-resistant asthma.

In vivo, 23 demonstrated anticancer efficacy comparable to that of the BKM120/JQ1 combination treatment in a KYSE450 xenograft mouse model. Significantly, the senolytic agent ABT737 enhanced the efficacy of compound 23 through the selective clearance of senescent cancer cells. Collectively, this work establishes 23 as a promising PI3K/BRD4 dual-targeting lead and supports senescence induction combined with senolytics as a novel strategy for esophageal cancer treatment.

The impact of YBX1 on the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was evaluated, and the effects of the PI3K inhibitor buparlisib (BKM120) on YBX1-driven cellular phenotypes were also tested...This study highlights the oncogenic role of YBX1 in CRC and reveals a potential YBX1-PI3K/AKT regulatory axis that may serve as a promising therapeutic target. The findings suggest that targeting this axis could provide a novel strategy for CRC treatment, especially under hypoxic or microenvironmental stress conditions.

In this study, we investigated the effects of conventional chemotherapeutics, Cisplatin and 5-fluorouracil (5-FU), in combination with small molecule inhibitors (SMIs) targeting the PI3K/AKT signaling pathway, on NSCLC cell viability...Dose-response analyses were performed to determine the optimal concentrations of Cisplatin, 5-FU, the AKT inhibitor MK2206, and the PI3K inhibitor BKM120, both as monotherapies and in combination treatments...Mechanistic studies revealed that apoptosis induction was mediated through the apoptotic pathway regulated by the Bcl-2 family and activation of caspase-3 and caspase-6. These findings highlight the therapeutic potential of combining PI3K/AKT inhibitors with conventional chemotherapy to overcome resistance mechanisms in NSCLC.

The effects of autophagy and proteasome inhibition were further examined using chloroquine and bortezomib, respectively. Moreover, our real-time PCR analysis provided evidence that the combination treatment not only down-regulated Bcl-2 expression but also upregulated BAD and BAX expression in A549 cells, which ultimately led to apoptotic-mediated cell death. In conclusion, this investigation illuminated the role of PI3K inhibition in the chemo-sensitivity of 549 cells and revealed that the combination of BKM120 and Cisplatin may represent a viable therapeutic option for NSCLC.

P1, N=47, Completed, Adlai Nortye Biopharma Co., Ltd. | Active, not recruiting --> Completed

Our study combines MRTX1133 with the SHP2 inhibitor SHP099 or PI3K inhibitor Buparlisib, showing synergistic inhibition of pancreatic cancer cell growth and enhanced apoptosis. These combination therapies could improve clinical outcomes for patients with KRAS G12D  mutation in pancreatic cancer.

LOGIC 2 supports the use of encorafenib plus binimetinib for treatment naive and previously treated locally advanced unresectable or metastatic BRAF V600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance.