alpelisib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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

Approvals:

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

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 2465.81 27.78 654 8152 41213 63439003
Rash 602.50 27.78 543 8263 560328 62919888
Blood glucose increased 572.72 27.78 263 8543 83493 63396723
Malignant neoplasm progression 543.07 27.78 252 8554 81869 63398347
Metastases to bone 239.37 27.78 95 8711 20924 63459292
Metastases to liver 231.95 27.78 96 8710 23543 63456673
Death 214.88 27.78 261 8545 374120 63106096
Diarrhoea 194.07 27.78 350 8456 715016 62765200
Diabetic ketoacidosis 176.85 27.78 76 8730 20429 63459787
Diabetes mellitus 119.59 27.78 82 8724 55728 63424488
Hyperglycaemic hyperosmolar nonketotic syndrome 110.54 27.78 26 8780 963 63479253
Disease progression 83.97 27.78 94 8712 122664 63357552
Mucosal inflammation 77.72 27.78 59 8747 46869 63433347
Decreased appetite 75.27 27.78 129 8677 250923 63229293
Blood glucose abnormal 73.80 27.78 31 8775 7861 63472355
Skin toxicity 70.45 27.78 26 8780 4688 63475528
Ketoacidosis 68.58 27.78 25 8781 4353 63475863
Metastases to lung 68.34 27.78 34 8772 12716 63467500
Weight decreased 66.21 27.78 129 8677 276669 63203547
Stomatitis 60.76 27.78 85 8721 138640 63341576
Nausea 59.98 27.78 255 8551 854216 62626000
PIK3CA-activated mutation 59.21 27.78 16 8790 1043 63479173
Glycosylated haemoglobin increased 51.88 27.78 28 8778 12370 63467846
Polydipsia 50.85 27.78 19 8787 3545 63476671
Carbohydrate antigen 15-3 increased 49.91 27.78 15 8791 1433 63478783
Laryngitis viral 45.96 27.78 8 8798 60 63480156
Metastases to pleura 44.39 27.78 14 8792 1571 63478645
Breast cancer metastatic 41.71 27.78 24 8782 11994 63468222
Tumour marker increased 38.38 27.78 17 8789 4898 63475318
Vomiting 37.49 27.78 165 8641 559452 62920764
Colitis 36.31 27.78 39 8767 48489 63431727
Hepatic lesion 35.47 27.78 16 8790 4809 63475407
Bone lesion 35.46 27.78 17 8789 5864 63474352
Metastases to central nervous system 34.70 27.78 22 8784 13083 63467133
Oral pain 32.87 27.78 29 8777 28365 63451851
Joint swelling 31.82 27.78 4 8802 327662 63152554
Arthralgia 31.74 27.78 20 8786 569690 62910526
Pyrexia 31.67 27.78 139 8667 470339 63009877
Dry mouth 30.09 27.78 45 8761 77818 63402398
Off label use 28.53 27.78 31 8775 674431 62805785
Rash maculo-papular 28.12 27.78 28 8778 31868 63448348

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 103.00 43.35 27 182 39453 34917269

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 1139.61 28.10 348 5393 69987 79668660
Malignant neoplasm progression 362.32 28.10 182 5559 135808 79602839
Blood glucose increased 354.37 28.10 170 5571 114805 79623842
Rash 269.63 28.10 264 5477 578094 79160553
Metastases to bone 212.48 28.10 76 5665 24351 79714296
Metastases to liver 197.90 28.10 75 5666 28239 79710408
Diarrhoea 134.93 28.10 232 5509 880257 78858390
Diabetic ketoacidosis 128.10 28.10 58 5683 34064 79704583
Death 109.18 28.10 166 5575 566348 79172299
Diabetes mellitus 85.37 28.10 59 5682 78331 79660316
PIK3CA-activated mutation 66.93 28.10 14 5727 589 79738058
Metastases to lung 62.25 28.10 29 5712 18134 79720513
Nausea 60.88 28.10 178 5563 957018 78781629
Mucosal inflammation 59.93 28.10 47 5694 75533 79663114
Skin toxicity 54.35 28.10 21 5720 8293 79730354
Laryngitis viral 51.20 28.10 8 5733 60 79738587
Weight decreased 49.19 28.10 90 5651 355108 79383539
Polydipsia 47.91 28.10 18 5723 6587 79732060
Decreased appetite 47.71 28.10 87 5654 342331 79396316
Carbohydrate antigen 15-3 increased 47.51 28.10 12 5729 1167 79737480
Breast cancer metastatic 39.95 28.10 17 5724 8585 79730062
Blood glucose abnormal 39.74 28.10 18 5723 10548 79728099
Hyperglycaemic hyperosmolar nonketotic syndrome 39.56 28.10 12 5729 2291 79736356
Stomatitis 35.34 28.10 48 5693 146709 79591938
Metastases to pleura 35.05 28.10 10 5731 1544 79737103
Dry mouth 34.71 28.10 37 5704 87982 79650665
Vomiting 33.97 28.10 115 5626 665713 79072934
Metastases to central nervous system 32.27 28.10 18 5723 16357 79722290
Bone lesion 31.87 28.10 13 5728 5906 79732741
Glycosylated haemoglobin increased 29.55 28.10 18 5723 19242 79719405
Fatigue 29.23 28.10 138 5603 929589 78809058
Tumour marker increased 28.67 28.10 11 5730 4261 79734386

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

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 POSTMENOPAUSAL WOMEN, AND MEN, 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 POSTMENOPAUSAL WOMEN, AND MEN, 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 POSTMENOPAUSAL WOMEN, AND MEN, WITH HR-POSITIVE, HER-2-NEGATIVE, PIK3CA-MUTATED, ADVANCED OR METASTATIC BREAST CANCER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
150MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL May 24, 2024 NEW CHEMICAL ENTITY
200MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL May 24, 2024 NEW CHEMICAL ENTITY
50MG PIQRAY NOVARTIS N212526 May 24, 2019 RX TABLET ORAL May 24, 2024 NEW CHEMICAL ENTITY
125MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL May 24, 2024 NEW CHEMICAL ENTITY
200MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL May 24, 2024 NEW CHEMICAL ENTITY
50MG VIJOICE NOVARTIS N215039 April 5, 2022 RX TABLET ORAL May 24, 2024 NEW CHEMICAL ENTITY
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
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
C4055478 UMLSCUI
1LT PDB_CHEM_ID
CHEMBL2396661 ChEMBL_ID
56649450 PUBCHEM_CID
DB12015 DRUGBANK_ID
D11011 KEGG_DRUG
9833 INN_ID
7955 IUPHAR_LIGAND_ID
018005 NDDF
788050002 SNOMEDCT_US
788079009 SNOMEDCT_US
4038445 VANDF
2169285 RXNORM
317932 MMSL
358240 MMSL
37038 MMSL
d09294 MMSL
C585539 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
PIQRAY HUMAN PRESCRIPTION DRUG LABEL 1 0078-0701 TABLET 200 mg ORAL NDA 31 sections
PIQRAY HUMAN PRESCRIPTION DRUG LABEL 1 0078-0701 TABLET 200 mg ORAL NDA 31 sections
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
PIQRAY HUMAN PRESCRIPTION DRUG LABEL 1 0078-0708 TABLET 150 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 30 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1021 TABLET 50 mg ORAL NDA 30 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1028 TABLET 125 mg ORAL NDA 30 sections
VIJOICE HUMAN PRESCRIPTION DRUG LABEL 1 0078-1028 TABLET 125 mg ORAL NDA 30 sections