alpelisib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
phosphatidylinositol 3-kinase inhibitors, antineoplastics 5328 1217486-61-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • alpelisib
  • piqray
  • BYL-719
  • NVP-BYL-719
  • vijoice
Alpelisib is an inhibitor of phosphatidylinositol-3- kinase (PI3K) with inhibitory activity predominantly against PI3Kalpha. Gain-of-function mutations in the gene encoding the catalytic alpha-subunit of PI3K (PIK3CA) lead to activation of PI3Kalpha and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models.
  • Molecular weight: 441.47
  • Formula: C19H22F3N5O2S
  • CLOGP: 2.47
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 101.21
  • ALOGS: -4.92
  • ROTB: 5
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.30 g O

ADMET properties:

PropertyValueReference
S (Water solubility) 0.02 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.188 Moderate 0.68
caco2-efflux Caco-2 efflux ratio (BA/AB) 9.290 Moderate 0.68
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 36.983 10^-6 cm/s Moderate 0.68
dh-clint Dog hepatocyte intrinsic clearance 1.507 uL/min/10^6 cells Moderate 0.68
dppb Dog plasma protein binding (% unbound) 8.790 % Moderate 0.68
fcs-ppb Fetal calf serum protein binding (% unbound) 16.960 % Moderate 0.68
herg hERG pIC50 5.015 pIC50 Moderate 0.68
hh-clint Human hepatocyte intrinsic clearance 1.242 uL/min/10^6 cells Moderate 0.68
hlm-clint Human liver microsomal intrinsic clearance 4.797 uL/min/mg protein Moderate 0.68
hppb Human plasma protein binding (% unbound) 9.520 % Moderate 0.68
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,CAMK2B,CAMK2D,CDK1,CDK9,CLK4,CSF1R,DDR1,DYRK1B,ERBB2,FLT3,GAK,GRK2,ITK,MAP3K1,MAP3K10,MAP3K21,MAP4K1,MAPK10,MAPK7,MARK4,MTOR,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKDC,SIK2,SIK3,STK17A,STK33,TGFBR1,ULK1 40
kinase-selectivity-class ACVR2B,AURKA,AXL,BRAF,CAMK2D,CDK1,CDK9,CLK4,DDR1,DYRK1A,DYRK1B,EGFR,FLT3,GRK2,JAK1,KDR,KIT,MAP3K10,MAP3K21,MAP4K1,MAPK7,MTOR,PDK1,PIK3CA,PIK3CD,PIK3CG,PRKDC,SIK2,SIK3,ULK1 30
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 11.641 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 25.586 Moderate 0.68
mh-clint Mouse hepatocyte intrinsic clearance 3.436 Moderate 0.68
mppb Mouse plasma protein binding (% unbound) 9.190 Moderate 0.68
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 29.512 Moderate 0.68
pfas-class PFAS structural alert (1 = True, 0 = False) 1
pppb Pig plasma protein binding (% unbound) 12.810 % Moderate 0.68
rat-kpuu-brain Rat brain Kpuu 0.028 % High 1
rh-clint Rat hepatocyte intrinsic clearance 1.774 uL/min/10^6 cells Moderate 0.68
rh-fuinc Rat hepatocyte fraction unbound in incubation 53.390 % Moderate 0.68
rppb Rat plasma protein binding (% unbound) 7.880 % Moderate 0.68
solubility-dd Solubility at pH 7.4 in DMSO 30.200 uM Moderate 0.68

Approvals:

DateAgencyCompanyOrphan
April 24, 2019 FDA NOVARTIS PHARMS CORP
July 27, 2020 EMA Novartis Europharm Limited

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperglycaemia 3105.74 27.87 799 10399 50171 90567078
Malignant neoplasm progression 822.02 27.87 352 10846 106518 90510731
Blood glucose increased 687.02 27.87 300 10898 94946 90522303
Rash 647.42 27.87 628 10570 795472 89821777
Metastases to bone 316.88 27.87 119 11079 25386 90591863
Death 305.58 27.87 326 10872 456225 90161024
Metastases to liver 299.28 27.87 118 11080 28689 90588560
Diabetic ketoacidosis 267.69 27.87 104 11094 24303 90592946
Diarrhoea 227.47 27.87 410 10788 938780 89678469
Diabetes mellitus 199.83 27.87 115 11083 64760 90552489
Disease progression 133.71 27.87 128 11070 156487 90460762
Blood glucose abnormal 120.39 27.87 45 11153 9447 90607802
Hyperglycaemic hyperosmolar nonketotic syndrome 115.26 27.87 28 11170 1341 90615908
Mucosal inflammation 106.57 27.87 74 11124 57551 90559698
PIK3CA-activated mutation 103.28 27.87 25 11173 1179 90616070
Weight decreased 89.98 27.87 165 11033 379745 90237504
Breast cancer metastatic 84.46 27.87 40 11158 15092 90602157
Decreased appetite 83.49 27.87 159 11039 376381 90240868
Skin toxicity 81.83 27.87 31 11167 6748 90610501
Glycosylated haemoglobin increased 77.37 27.87 38 11160 15524 90601725
Metastases to pleura 76.55 27.87 22 11176 2022 90615227
Metastases to lung 73.44 27.87 37 11161 15954 90601295
Ketoacidosis 72.68 27.87 27 11171 5568 90611681
Carcinoembryonic antigen increased 69.21 27.87 21 11177 2329 90614920
Nausea 69.18 27.87 295 10903 1110021 89507228
Polydipsia 60.82 27.87 22 11176 4209 90613040
Carbohydrate antigen 15-3 increased 59.39 27.87 18 11180 1989 90615260
Tumour marker increased 54.04 27.87 22 11176 5785 90611464
Joint swelling 47.36 27.87 4 11194 503296 90113953
Activated PI3 kinase delta syndrome 44.82 27.87 8 11190 80 90617169
Laryngitis viral 44.73 27.87 8 11190 81 90617168
Pneumonitis 43.20 27.87 39 11159 44131 90573118
Metastases to lymph nodes 42.13 27.87 23 11175 11666 90605583
Hepatic lesion 41.14 27.87 18 11180 5655 90611594
Arthralgia 39.11 27.87 24 11174 778498 89838751
Bone lesion 38.96 27.87 18 11180 6419 90610830
Polyuria 36.86 27.87 20 11178 10020 90607229
Oral pain 36.25 27.87 31 11167 32652 90584597
Vomiting 36.11 27.87 192 11006 788101 89829148
Blood creatinine increased 36.05 27.87 53 11145 101333 90515916
Stomatitis 35.86 27.87 94 11104 274604 90342645
Dehydration 35.67 27.87 76 11122 194371 90422878
Metastases to central nervous system 33.51 27.87 23 11175 17519 90599730
Maternal exposure during pregnancy 33.48 27.87 3 11195 360060 90257189
Colitis 33.10 27.87 42 11156 69900 90547349
Rash maculo-papular 32.13 27.87 32 11166 40901 90576348
Pleural effusion 32.08 27.87 53 11145 111938 90505311
Therapy interrupted 30.14 27.87 34 11164 50074 90567175
Hypoglycaemia 30.02 27.87 40 11158 69808 90547441
Drug hypersensitivity 29.93 27.87 10 11188 463599 90153650
Pyrexia 29.60 27.87 160 11038 660325 89956924
Sinusitis 29.02 27.87 4 11194 343084 90274165
Fatigue 28.51 27.87 241 10957 1153782 89463467
Ascites 28.04 27.87 32 11166 47708 90569541

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperglycaemia 157.59 50.97 44 401 45815 42575075

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperglycaemia 1564.81 28.52 462 7330 84628 110496879
Malignant neoplasm progression 552.66 28.52 261 7531 174306 110407201
Blood glucose increased 418.42 28.52 198 7594 132298 110449209
Rash 302.02 28.52 327 7465 820637 109760870
Metastases to bone 265.03 28.52 95 7697 31277 110550230
Metastases to liver 242.96 28.52 92 7700 35294 110546213
Diabetic ketoacidosis 180.42 28.52 78 7714 41980 110539527
Diarrhoea 168.23 28.52 292 7500 1139213 109442294
Death 149.94 28.52 213 7579 698656 109882851
Diabetes mellitus 122.21 28.52 80 7712 99301 110482206
PIK3CA-activated mutation 100.96 28.52 20 7772 653 110580854
Mucosal inflammation 84.47 28.52 63 7729 96078 110485429
Breast cancer metastatic 80.03 28.52 30 7762 11151 110570356
Blood glucose abnormal 75.83 28.52 30 7762 12886 110568621
Metastases to lung 68.05 28.52 33 7759 23030 110558477
Weight decreased 65.88 28.52 118 7674 467939 110113568
Nausea 65.66 28.52 213 7579 1235477 109346030
Skin toxicity 64.42 28.52 26 7766 11757 110569750
Polydipsia 60.06 28.52 22 7770 7666 110573841
Carcinoembryonic antigen increased 58.83 28.52 17 7775 2807 110578700
Carbohydrate antigen 15-3 increased 58.61 28.52 15 7777 1572 110579935
Laryngitis viral 50.17 28.52 8 7784 71 110581436
Disease progression 49.94 28.52 73 7719 243961 110337546
Decreased appetite 48.73 28.52 105 7687 475741 110105766
Glycosylated haemoglobin increased 47.17 28.52 26 7766 23593 110557914
Hyperglycaemic hyperosmolar nonketotic syndrome 44.89 28.52 14 7778 2995 110578512
Tumour marker increased 41.46 28.52 15 7777 5045 110576462
Metastases to pleura 41.12 28.52 12 7780 2051 110579456
Growth retardation 38.46 28.52 12 7780 2570 110578937
Vomiting 34.56 28.52 141 7651 910534 109670973
Polyuria 33.98 28.52 19 7773 17719 110563788
Osteonecrosis of jaw 32.50 28.52 27 7765 47990 110533517
Bone lesion 29.88 28.52 13 7779 7074 110574433

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EM03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Phosphatidylinositol-3-kinase (Pi3K) inhibitors

Related Drugs by ATC class:

L01EM Phosphatidylinositol-3-kinase (Pi3K) inhibitors 4 drugs
copanlisibduvelisibidelalisibinavolisib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
PIK3CA-related overgrowth spectrum (PROS) indication 737037004
Germline BRCA-mutated, HER2-negative metastatic breast cancer indication 767444009




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.6 acidic
pKa2 13.49 acidic
pKa3 5.2 Basic
pKa4 2.4 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
150MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL 8227462 April 29, 2033 IN COMBINATION WITH FULVESTRANT FOR TREATMENT OF ADULTS WITH HR-POSITIVE, HER-2-NEGATIVE, PIK3CA-MUTATED, ADVANCED OR METASTATIC BREAST CANCER
200MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL 8227462 April 29, 2033 IN COMBINATION WITH FULVESTRANT FOR TREATMENT OF ADULTS WITH HR-POSITIVE, HER-2-NEGATIVE, PIK3CA-MUTATED, ADVANCED OR METASTATIC BREAST CANCER
50MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL 8227462 April 29, 2033 IN COMBINATION WITH FULVESTRANT FOR TREATMENT OF ADULTS WITH HR-POSITIVE, HER-2-NEGATIVE, PIK3CA-MUTATED, ADVANCED OR METASTATIC BREAST CANCER
125MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL 11433059 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY AND IS NOT RESPONSIVE TO RAPAMYCIN
125MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL 12427141 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY
200MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL 11433059 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY AND IS NOT RESPONSIVE TO RAPAMYCIN
200MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL 12427141 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY
50MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL 11433059 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY AND IS NOT RESPONSIVE TO RAPAMYCIN
50MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL 12427141 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY
50MG/PACKET VIJOICE NOVARTIS N218466 April 24, 2024 RX GRANULE ORAL 11433059 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY AND IS NOT RESPONSIVE TO RAPAMYCIN
50MG/PACKET VIJOICE NOVARTIS N218466 April 24, 2024 RX GRANULE ORAL 12427141 Feb. 17, 2037 TREATMENT OF SEVERE PHOSPHATIDYLINOSITOL-3-KINASE CATALYTIC SUBUNIT ALPHA (PIK3CA)-RELATED OVERGROWTH SPECTRUM (PROS) HAVING AN OVERGROWTH OF MULTIPLE TISSUES, THAT REQUIRES SYSTEMIC THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
150MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL Jan. 18, 2027 EXPANSION OF THE INDICATION TO INCLUDE PRE AND PERIMENOPAUSAL WOMEN
200MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL Jan. 18, 2027 EXPANSION OF THE INDICATION TO INCLUDE PRE AND PERIMENOPAUSAL WOMEN
50MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL Jan. 18, 2027 EXPANSION OF THE INDICATION TO INCLUDE PRE AND PERIMENOPAUSAL WOMEN
125MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL April 5, 2029 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH SEVERE MANIFESTATIONS OF PIK3CA-RELATED OVERGROWTH SPECTRUM (PROS) WHO REQUIRE SYSTEMIC THERAPY
200MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL April 5, 2029 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH SEVERE MANIFESTATIONS OF PIK3CA-RELATED OVERGROWTH SPECTRUM (PROS) WHO REQUIRE SYSTEMIC THERAPY
50MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL April 5, 2029 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH SEVERE MANIFESTATIONS OF PIK3CA-RELATED OVERGROWTH SPECTRUM (PROS) WHO REQUIRE SYSTEMIC THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kinase INHIBITOR IC50 8.34 SCIENTIFIC LITERATURE DRUG LABEL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Kinase IC50 6.54 CHEMBL
Cyclin-G-associated kinase Kinase Kd 5.30 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Kinase IC50 5.92 CHEMBL
Serine/threonine-protein kinase mTOR Kinase IC50 5.52 CHEMBL
Phosphatidylinositol 4-kinase beta Kinase IC50 7.41 CHEMBL
cAMP-dependent protein kinase catalytic subunit gamma Kinase Kd 5.70 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Kinase IC50 6.60 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Kinase IC50 5.66 CHEMBL

External reference:

IDSource
08W5N2C97Q UNII
4038445 VANDF
C4055478 UMLSCUI
1LT PDB_CHEM_ID
CHEMBL2396661 ChEMBL_ID
56649450 PUBCHEM_CID
DB12015 DRUGBANK_ID
D11011 KEGG_DRUG
9833 INN_ID
C585539 MESH_SUPPLEMENTAL_RECORD_UI
7955 IUPHAR_LIGAND_ID
788050002 SNOMEDCT_US
788079009 SNOMEDCT_US
CHEBI:231324 CHEBI
317932 MMSL
358240 MMSL
37038 MMSL
d09294 MMSL
018005 NDDF
2169285 RXNORM
08W5N2C97Q INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
PIQRAY HUMAN PRESCRIPTION DRUG LABEL 1 0078-0701 TABLET 200 mg ORAL NDA 31 sections
PIQRAY HUMAN PRESCRIPTION DRUG LABEL 1 0078-0708 TABLET 150 mg ORAL NDA 31 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1021 TABLET 50 mg ORAL NDA 31 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1021 TABLET 50 mg ORAL NDA 31 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1028 TABLET 125 mg ORAL NDA 31 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1028 TABLET 125 mg ORAL NDA 31 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1175 GRANULE 50 mg ORAL NDA 31 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1175 GRANULE 50 mg ORAL NDA 31 sections