buparlisib (AN2025)

Combining SDUY104 with an ERK inhibitor Ulixertinib produced synergistic antiproliferative activity via enhanced MAPK suppression. In a PANC-1 xenograft model, combination of SDUY104 with BKM-120 exhibited superior antitumor activity compared to either monotherapy. Collectively, this study identifies a potent SHP2 allosteric inhibitor and delineates a critical compensatory signaling mechanism underlying resistance to SHP2-targeted therapy, providing proof-of-concept support for pancreatic cancer treatment.

Although the trial met the primary endpoint, buparlisib monotherapy was associated with unacceptable toxicity and showed limited efficacy in heavily pretreated HNSCC patients.

High TRPRS was associated with diminished cytotoxic T-cell infiltration and predicted resistance to multiple therapeutics-including cisplatin, carmustine, gefitinib, buparlisib, and afatinib. Functional assays demonstrated that IFNGR2 knockdown suppressed glioma cell proliferation and attenuated NF-κB signaling, underscoring its role as a key driver within the TRP network. TRPRS provides a robust, biologically grounded tool for simultaneous prognostication and therapy guidance in GBM, highlighting TRP signaling as a therapeutic vulnerability.

P1/2, N=24, Terminated, Institut Paoli-Calmettes | N=106 --> 24 | Suspended --> Terminated; Drug development withdrawn

This study evaluated three potential anticancer agents targeting these pathways: buparlisib (a pan-PI3K/mTORC1 inhibitor), SN32976 (a PI3K p110α inhibitor), and pterostilbene (a resveratrol analogue that downregulates PI3K/AKT and NFκB signaling)...Growth in 3D collagen gels conferred drug resistance on OVCAR8 but not SKOV3 models. Overall, these findings provide preclinical support for further investigation of SN32976 and pterostilbene in ovarian cancer models.

Cediranib demonstrated synergy with BKM120, significantly reducing organoid growth. It highlights that high-throughput sequencing for individual patient tumors and generation of patient-derived models are feasible in endometrial cancer. This preclinical model may assist clinical decision and personalized therapy requiring validation in prospective studies.

Validation revealed a substantial reduction in cell viability for the majority of perturbagens in most cell types. Our result observed significantly overexpressed phosphorylation sites within the AKT1 and PI3K genes, which are buparlisib target genes, suggesting that buparlisib may exert its effects across a spectrum of breast cancer types, including triple-negative breast cancer, by modulating molecular mechanisms within the PI3K pathway.

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.