alpelisib   Click here for help

GtoPdb Ligand ID: 7955

Synonyms: BYL 719 | BYL-719 | NVP-BYL719 | Piqray®
Approved drug PDB Ligand
alpelisib is an approved drug (FDA (2019), FDA (2020))
Compound class: Synthetic organic
Comment: Alpelisib is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor that exhibits antineoplastic activity. It is selective for the α isoform (PIK3CA). It was the first PIK3CA inhibitor to be approved for the treatment of breast cancer.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 129.45
Molecular weight 441.14
XLogP 1.82
No. Lipinski's rules broken 0
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Canonical SMILES NC(=O)C1CCCN1C(=O)Nc1nc(c(s1)c1ccnc(c1)C(C(F)(F)F)(C)C)C
Isomeric SMILES NC(=O)[C@@H]1CCCN1C(=O)Nc1nc(c(s1)c1ccnc(c1)C(C(F)(F)F)(C)C)C
InChI InChI=1S/C19H22F3N5O2S/c1-10-14(11-6-7-24-13(9-11)18(2,3)19(20,21)22)30-16(25-10)26-17(29)27-8-4-5-12(27)15(23)28/h6-7,9,12H,4-5,8H2,1-3H3,(H2,23,28)(H,25,26,29)/t12-/m0/s1
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Summary of Clinical Use Click here for help
Multiple clinical trials are assessing alpelisib in a range of PIK3CA mutated solid and haematologic cancers, either as a monotherapy or in combination with established and/or novel oncology drugs. Click here to link to's full list of alpelisib trials. A combination therapy of alpelisib and fulvestrant was FDA approved in May 2019 [3], as a treatment for men and postmenopausal women with HR+ve, HER2-ve, PIK3CA-mutated advanced/metastatic breast cancer that has progressed on or after an endocrine-based therapy.

CLOVES syndrome is a genetic disorder that results from gain-of-function mutations of the PIK3CA gene (e.g. the H1047R mutation), and is one of a spectrum of PIK3CA-related overgrowth syndromes. A study in France has demonstrated that targeted therapy with alpelisib produced substantial therapeutic effects in all nineteen CLOVES patients included in the trial [4].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Alpelisib selectively inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This results in inhibition of tumour cell growth and survival in susceptible tumour cell populations.