Drug intelligence / Profile preview

alpelisib + luminespib

Development stage
Phase 1
Lead developer
Novartis
Modality
Small Molecules
Administration
Oral
01

Overview

**Alpelisib + luminespib** is a combination of two targeted small molecule drugs: - **Alpelisib** is a phosphatidylinositol 3-kinase (PI3K) alpha isoform inhibitor that suppresses PI3K/AKT/mTOR signaling, a pathway commonly activated in many cancers due to mutations such as PIK3CA. - **Luminespib** (code name AUY922) is a potent inhibitor of heat shock protein 90 (HSP90), a molecular chaperone required for stability and function of multiple oncogenic client proteins, including kinases and transcription factors relevant in cancer progression. This combination is investigated for synergistic anti-tumor activity, leveraging PI3K pathway blockade and inhibition of HSP90-dependent protein folding, which together may overcome resistance to monotherapies and inhibit tumor proliferation more effectively than either agent alone. The combination has been studied in early-phase clinical trials for advanced solid tumors, particularly those harboring PI3K pathway alterations or displaying resistance to monotherapy. Key adverse events are consistent with known toxicities of PI3K inhibitors (such as hyperglycemia, rash, gastrointestinal disturbances) and HSP90 inhibitors (ocular toxicity, liver enzyme elevations, gastrointestinal symptoms)[2].

Brand names
PIQRAY (alpelisib)
Other names
alpelisib + AUY922BYL719 + AUY922alpelisib + luminespib
02

Targets

HSP90AA1 (Heat shock protein HSP90-alpha)HSP90AB1 (Heat shock protein HSP 90-beta)PIK3CB (Phosphatidylinositol 3-kinase beta subunit)PIK3CG (Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma)PIK3CD (Phosphatidylinositol 3-kinase delta)PIK3CA (Phosphoinositide 3-kinase alpha)

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