General
Preferred name
ALPELISIB
Synonyms
BYL-719 ()
Alpelisib, NVP-BYL719 ()
BYL719 ()
A-1214 ()
(S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide ()
NVP-BYL719 ()
PIQRAY ()
VIJOICE ()
Alpelisib (BYL719) ()
P&D ID
PD003422
CAS
1217486-61-7
1217486-47-9
Tags
available
drug
probe
Approved by
FDA
EMA
First approval
2019
Drug indication
Solid tumour/cancer
Breast cancer
Drug Status
approved
investigational
Max Phase
4.0
Probe info
Probe selectivity
protein-selective
Probe type
experimental probe
P&D approved
calculated probe
Probe sources
Chemical Probes.org
High-quality chemical probes
Tool Compound Set
Probe targets
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION Alpelisib is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. The inhibitor is selective for the α isoform.
HALF-LIFE The mean half life of alprelisib is 8 to 9 hours.[Label]
ROE 36% of an oral dose is eliminated as unchanged drug in the feces and 32% as the primary metabolite BZG791 in the feces.[Label] 2% of an oral dose is eliminated in the urine as unchanged drug and 7.1% as the primary metabolite BZG791.[Label] In total 81% of an oral dose is eliminated in the feces and 14% is eliminated in the urine.[Label]
PHARMACODYNAMICS Alpelisib does not prolong the QTcF interval.[Label] Patients taking alpelisib experience a dose dependent benefit from treatment with a 51% advantage of a 200mg daily dose over a 100mg dose and a 22% advantage of 300mg once daily over 150mg twice daily.[A179260] This suggests patients requiring a lower dose may benefit from twice daily dosing.[A179260]
MOA Phosphatidylinositol-3-kinase-α (PI3Kα) is responsible for cell proliferation in response to growth factor-tyrosine kinase pathway activation.[A179209] In some cancers PI3Kα's p110α catalytic subunit is mutated making it hyperactive.[A179209] Alpelisib inhibits (PI3K), with the highest specificity for PI3Kα.[Label]
INDICATION Alpelisib is indicated in combination with fulvestrant to treat postmenopausal women, and men, with advanced or metastatic breast cancer.[Label] This cancer must be hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and PIK3CA­ mutated.[Label] The cancer must be detected by an FDA-approved test following progression on or after an endocrine-based regimen.[Label]
TOXICITY **LD50 and Overdose**; ; Patients experiencing an overdose may present with hyperglycemia, nausea, asthenia, and rash.[Label] There is no antidote for an overdose of alpelisib so patients should be treated symptomatically.[Label]; Data regarding an LD50 is not readily available.[MSDS] In clinical trials, patients were given doses of up to 450mg once daily.[Label]; ; **Pregnancy, Lactation, and Fertility**; ; Following administration in rats and rabbits during organogenesis, adverse effects on the reproductive system, such as embryo-fetal mortality, reduced fetal weights, and increased incidences of fetal malformations, were observed.[Label]; Based on these findings of animals studies and its mechanism of action, it is proposed that alpelisib may cause embryo-fetal toxicity when administered to pregnant patients.[Label]; There is no data available regarding the presence of alpelisib in breast milk so breast feeding mothers are advised not to breastfeed while taking this medication and for 1 week after their last dose.[Label]; Based on animal studies, alpelisib may impair fertility of humans.[Label]; ; **Carcinogenicity and Mutagenicity**; ; Studies of carcinogenicity have yet to be performed.[Label] Alpelisib has not been found to be mutagenic in the Ames test.[Label] It is not aneugenic, clastogenic, or genotoxic in further assays.[Label]
ABSORPTION Alpelisib reached a peak concentration in plasma of 1320±912ng/mL after 2 hours.[A179254] Alpelisib has an AUClast of 11,100±3760h ng/mL and an AUCINF of 11,100±3770h ng/mL.[A179254] A large, high fat meal increases the AUC by 73% and Cmax by 84% while a small, low fat meal increases the AUC by 77% and Cmax by 145%.[Label]
COMMENT Chemical Neighbourhood for QSAR: 15 molecules similar (>0.80) to BYL-719 with in vitro affinities for PIK3CA were found in public repositories (e.g., ChEMBL). Jul 13 2016 - 4:20pm
DESCRIPTION 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. (GtoPdb)
METABOLISM Alpelisib is metabolized by hydrolysis reactions to form the primary metabolite.[Label] It is also metabolized by CYP3A4.[Label] The full metabolism of Alpelisib has yet to be determined but a series of reactions have been proposed.[A179254,A179257] The main metabolic reaction is the substitution of an amine group on alpelisib for a hydroxyl group to form a metabolite known as M4[A179254,A179257] or BZG791.[Label] Alpelisib can also be glucuronidated to form the M1 and M12 metabolites.[A179254,A179257]
MOA ATP-competitive inhibitor (Chemical Probes.org)
DESCRIPTION inhibitor of PI3K catalytic subunit alpha (Informer Set)
DESCRIPTION On may 2019, FDA approved alpelisib to treat breast cancer (PKIDB)
Cell lines
7
Organisms
0
Compound Sets
37
AdooQ Bioactive Compound Library
A11328
Axon Medchem Screening Library
2925
Cayman Chemical Bioactives
16986
ChEMBL Approved Drugs
CHEMBL2396661
ChEMBL Drugs
CHEMBL2396661
Chemical Probes.org
byl-719
Clinical kinase drugs
Concise Guide to Pharmacology 2017/18
7955
Concise Guide to Pharmacology 2019/20
7955
Concise Guide to Pharmacology 2021/22
7955
Concise Guide to Pharmacology 2023/24
7955
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB12015
DrugBank Approved Drugs
DB12015
DrugCentral
5328
DrugCentral Approved Drugs
5328
DrugMAP
DMEXMYK
DrugMAP Approved Drugs
DMEXMYK
EU-OPENSCREEN Bioactive Compound Library
EOS101220
EUbOPEN Chemogenomics Library
EUB0000689
Guide to Pharmacology
7955
High-quality chemical probes
PD003422
Informer Set
668495
Kinase Inhibitors (best-in-class)
LINCS compound set
10233-101
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL2396661
MedChem Express Bioactive Compound Library
HY-15244
NCATS Inxight Approved Drugs
08W5N2C97Q
NIH Approved Oncology Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
byl719
TargetMol Bioactive Compound Library
T1921
Tool Compound Set
ZINC Tool Compounds
ZINC000068198368
External IDs
35
Properties
(calculated by RDKit )
Molecular Weight
441.14
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
2
Rotatable Bonds
4
Ring Count
3
Aromatic Ring Count
2
cLogP
3.84
TPSA
101.21
Fraction CSP3
0.47
Chiral centers
1.0
Largest ring
6.0
QED
0.75
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
PIK3CA
PI3Kα
PI3-kinase p110-alpha subunit
PI3K??
PIK3CA, PIK3CB, PIK3CD, PIK3CG
Compound status
clinical
Kinase group
Lipid
Pathway
PI3K/Akt/mTOR signaling
PI3K/Akt/mTOR
MOA
PI3K
PI3Kalpha inhibitor
PIK3CA inhibitor
PI3K inhibitor
Member status
virtual
Indication
breast cancer
Orthogonal probe
Pictilisib
Target class
Lipid kinase
Target subclass
Class I
Recommended Cell Concentration
1 µM
Source data