Details of the Drug

General Information of Drug (ID: DMEXMYK)

Drug Name
Alpelisib
Synonyms
alpelisib; 1217486-61-7; BYL-719; BYL719; UNII-08W5N2C97Q; BYL 719; Alpelisib (BYL719); (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; (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide; CHEMBL2396661; 08W5N2C97Q; AK146107; C19H22F3N5O2S; (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)-pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
ATC Code
L01EM03: Alpelisib
L01EM: Phosphatidylinositol-3-kinase (Pi3K) inhibitors
L01E: PROTEIN KINASE INHIBITORS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 441.5
Logarithm of the Partition Coefficient (xlogp) 3.2
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 11,100 +/- 3760 mcgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 1320 +/- 912 mcg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2 h [3]
Clearance
The apparent oral clearance of drug is 39.0 L/h [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 8 - 9 hours [4]
Metabolism
The drug is metabolized via the hydrolysis reactions [3]
Vd
The volume of distribution (Vd) of drug is 114 L []
Chemical Identifiers
Formula
C19H22F3N5O2S
IUPAC Name
(2S)-1-N-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
Canonical SMILES
CC1=C(SC(=N1)NC(=O)N2CCC[C@H]2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F
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
InChIKey
STUWGJZDJHPWGZ-LBPRGKRZSA-N
Cross-matching ID
PubChem CID
56649450
ChEBI ID
CHEMBL2396661
CAS Number
1217486-61-7
UNII
08W5N2C97Q
DrugBank ID
DB12015
TTD ID
D0W7HE
INTEDE ID
DR0074
ACDINA ID
D00827
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
PI3-kinase alpha (PIK3CA) TTEUNMR PK3CA_HUMAN Inhibitor [1]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 02 Neoplasm
Disease Class ICD-11: 2C82 Prostate cancer
The Studied Tissue Breast tissue
The Studied Disease Breast cancer [ICD-11:2C82]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
PI3-kinase alpha (PIK3CA) DTT PIK3CA 1.59E-38 -0.65 -1.11
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.87E-03 -6.67E-02 -2.12E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alpelisib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Moderate Increased metabolism of Alpelisib caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [6]
Ag-221 DMS0ZBI Moderate Decreased clearance of Alpelisib due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [7]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Alpelisib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [6]
Ripretinib DM958QB Moderate Decreased clearance of Alpelisib due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [7]
MK-1439 DM215WE Moderate Increased metabolism of Alpelisib caused by MK-1439 mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [6]
PF-06463922 DMKM7EW Moderate Increased metabolism of Alpelisib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [6]
Ubrogepant DM749I3 Moderate Decreased clearance of Alpelisib due to the transporter inhibition by Ubrogepant. Migraine [8A80] [8]
Rimegepant DMHOAUG Moderate Decreased clearance of Alpelisib due to the transporter inhibition by Rimegepant. Migraine [8A80] [9]
Siponimod DM2R86O Moderate Increased metabolism of Alpelisib caused by Siponimod mediated induction of CYP450 enzyme. Multiple sclerosis [8A40] [6]
Lefamulin DME6G97 Moderate Decreased metabolism of Alpelisib caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [10]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Alpelisib caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [6]
Larotrectinib DM26CQR Moderate Decreased clearance of Alpelisib due to the transporter inhibition by Larotrectinib. Solid tumour/cancer [2A00-2F9Z] [7]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Alpelisib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [11]
Betrixaban DM2C4RF Moderate Decreased clearance of Alpelisib due to the transporter inhibition by Betrixaban. Venous thromboembolism [BD72] [12]
⏷ Show the Full List of 14 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Ferric oxide black E00522 16211978 Colorant
Hypromellose E00634 Not Available Coating agent
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Haematite red E00236 14833 Colorant
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 9 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Alpelisib 50mg tablet 50mg Tablet Oral
Alpelisib 150mg tablet 150mg Tablet Oral
Alpelisib 200mg tablet 200mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7955).
3 Teramura T, Watanabe T, Higuchi S, Hashimoto K: Metabolism and pharmacokinetics of barnidipine hydrochloride, a calcium channel blocker, in man following oral administration of its sustained release formulation. Xenobiotica. 1997 Feb;27(2):203-16. doi: 10.1080/004982597240695 .
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Comparison of 19F NMR and 14C measurements for the assessment of ADME of BYL719 (Alpelisib) in humans. Drug Metab Dispos. 2017 Aug;45(8):900-907.
6 Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
7 Cerner Multum, Inc. "Australian Product Information.".
8 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
9 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
10 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
11 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
12 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.