Piqray (alpelisib)

To gain insights into PI3K/mTOR pathway dysregulation in this context, we perform a human genome-wide CRISPR/Cas9 screen for hits that synergistically blocked EBVaGC proliferation together with the PI3K antagonist alpelisib...Rather than perturbing mTORC1 lysosomal recruitment, ZMYND19 and MKLN1 block the interaction between mTORC1 and Rheb and also with mTORC1 substrates S6 and 4E-BP1. Thus, CTLH enables cells to rapidly tune mTORC1 activity at the lysosomal membrane via the ubiquitin/proteasome pathway.

P=N/A, N=600, Completed, Novartis Pharmaceuticals | Recruiting --> Completed | N=200 --> 600 | Trial completion date: Sep 2025 --> Feb 2025 | Trial primary completion date: Sep 2025 --> Feb 2025

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.

To address this, we developed a TME-responsive polymeric micelle co-delivering alpelisib (a pan-PI3K inhibitor) and cobomarsen (a miR-155-5p inhibitor) for targeted therapy. This dual-targeting strategy effectively suppressed PIK3CA-mutated tumor growth and epithelial-mesenchymal transition. These findings reveal the role of MDSC-driven metastatic potential via the exosomal miR-155-5p/SIRT1 axis in HR + breast cancer and present a novel nanotherapeutic approach for precision intervention.

mTOR and PI3Kα inhibitors such as sirolimus and alpelisib have shown promising efficacy in slow-flow VMs, while reports have suggested that MAPK inhibitors such as trametinib may improve arteriovenous malformations. Emerging approaches such as mutant-selective inhibitors, proteolysis-targeting chimeras, and gene therapy hold promises for improving treatment specificity and minimizing adverse effects. This review provides an overview of the genetic bases of VMs, recent advances in targeted therapies, and future directions in the field, highlighting the ongoing evolution of precision medicine for VMs.

Application to patient samples validated the method's clinical relevance, with measured concentrations aligning with the expected ones. This is the first capillary electrophoresis method for ALP in biological matrices and the only method for simultaneous TDM of ALP and FUL, offering a robust, cost-effective, and eco-friendly alternative to traditional chromatographic approaches.

Crucially, A32 (50 mg/kg) markedly reduced hyperglycemia risk versus alpelisib and displayed favorable pharmacokinetics. These findings establish A32 as a potent, selective, and metabolically safe PI3Kα inhibitor with a promising therapeutic profile.

LR group had lower TIDE scores and lower IC50 values (Alpelisib, Ibrutinib, Sapitinib, and Savolitinib). Patients in LR group had potential advantages in survival, immune response, and drug sensitivity. In summary, the results offered new insights into prognosis prediction, immunotherapy, and personalized treatment of LUSC.

Treatment with PI3K inhibitor alpelisib eradicates resistant cells in vitro and in vivo, with prolonged survival of leukemic mice through downregulation of F2R, ITGA2, and COL6A1. Thus, the lncRNA-m6A-PI3K cascade represents a new non-genetic predictor for drug resistance and poorer prognosis in cancer, and a pan-cancer mechanism underlying TKI resistance.

Recent studies have shown that alpelisib, a PI3Kα inhibitor initially designed for breast cancer, is also effective at treating PROS...In unrelated disorders indeed, PI3Kα involvement has been reported in various cell types such as mesangial, tubular and immune cells. This review aims at summarizing the available evidence on the involvement of the pathway in monogenic disorders and kidney disease, highlighting PI3Kα as a potential novel therapeutic target in various nephropathies.

P2/3, N=232, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2028 --> May 2028

P1/2, N=255, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2025 --> Feb 2027 | Trial primary completion date: Dec 2025 --> Feb 2027