Explore a selection of our essential drug information below, or:
Identification
- Brand Names
- Piqray 300 Mg Daily Dose, Vijoice 50 Mg 28 Day
- Generic Name
- Alpelisib
- DrugBank Accession Number
- DB12015
- Background
Alpelisib is a phosphatidylinositol 3-kinase (PI3K) inhibitor with potent antitumor activity. It works by selectively inhibiting class I PI3K p110α 2, which is the catalytic subunit of PI3K, a lipid kinase that plays a role in various biological processes, including proliferation, survival, differentiation, and metabolism. Alpelisib was designed to target this enzyme that appears to be mutated at a rate of nearly 30% in human cancers, leading to hyperactivation.3
There are several isoform-specific PI3K inhibitors that are under clinical development or currently approved, such as idelalisib used for chronic lymphocytic leukemia (CLL).3 Approved by the FDA in May 2019, alpelisib is the first approved PI3K inhibitor indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer in combination with fulvestrant for postmenopausal women and male patients. To initiate alpelisib therapy, it is required that the presence of a PIK3CA mutation in the tissue and/or liquid biopsy sample collection should be confirmed via FDA-approved diagnostic tests. Alpelisib is marketed under the trade name Piqray and is available as oral tablets. Studies evaluating the therapeutic effectiveness of alpelisib in other cancers, such as ovarian cancer 1 and colorectal cancer 2, are under ongoing investigations.
Alpelisib was granted FDA approval on 24 May 2019.7 In April 2022, the FDA granted the use of alpelisib in the treatment of PIK3CA-Related Overgrowth Spectrum (PROS) in adults and children who require systemic therapy.8
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Alpelisib (DB12015)
- Weight
- Average: 441.47
Monoisotopic: 441.144630278 - Chemical Formula
- C19H22F3N5O2S
- Synonyms
- Alpelisib
- External IDs
- BYL 719
- BYL-719
- BYL719
- NVP-BYL719
Pharmacology
- Indication
Alpelisib is indicated in combination with fulvestrant to treat postmenopausal women, and men, with advanced or metastatic breast cancer. This cancer must be hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and PIK3CA mutated. The cancer must be detected by an FDA-approved test following progression on or after an endocrine-based regimen.7
Alpelisib is also used to treat adult and pediatric patients two years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).8
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Pik3ca-related overgrowth spectrum (pros) •••••••••••• •••••• •••••••• ••••••••• ••••••• •••••••• ••••••• •••••• Used in combination to treat Advanced hr + her2 - breast cancer Regimen in combination with: Fulvestrant (DB00947) •••••••••••• •••••• •••••••••••••• •••••• •••• ••••••••• ••••••• ••••••••••• ••••• ••••••••• ••••• ••••••• •••••• Used in combination to treat Metastatic hr + her2 - breast cancer Regimen in combination with: Fulvestrant (DB00947) •••••••••••• •••••• •••••••••••••• ••••••• ••••••••••• ••••• ••••••••• ••••• •••••••• •••••• •••• •••••••• •••••• - Contraindications & Blackbox Warnings
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Alpelisib does not prolong the QTcF interval.7 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.6 This suggests patients requiring a lower dose may benefit from twice daily dosing.6
- Mechanism of action
Phosphatidylinositol-3-kinase-α (PI3Kα) is responsible for cell proliferation in response to growth factor-tyrosine kinase pathway activation.3 In some cancers PI3Kα's p110α catalytic subunit is mutated making it hyperactive.3 Alpelisib inhibits (PI3K), with the highest specificity for PI3Kα.7
Target Actions Organism APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform inhibitorHumans - Absorption
Alpelisib reached a peak concentration in plasma of 1320±912ng/mL after 2 hours.4 Alpelisib has an AUClast of 11,100±3760h ng/mL and an AUCINF of 11,100±3770h ng/mL.4 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%.7
- Volume of distribution
The apparent volume of distribution at steady state is 114L.7
- Protein binding
Alpelisib is 89% protein bound.7
- Metabolism
Alpelisib is metabolized by hydrolysis reactions to form the primary metabolite. It is also metabolized by CYP3A4.7 The full metabolism of Alpelisib has yet to be determined but a series of reactions have been proposed.4,5 The main metabolic reaction is the substitution of an amine group on alpelisib for a hydroxyl group to form a metabolite known as M44,5 or BZG791.7 Alpelisib can also be glucuronidated to form the M1 and M12 metabolites.4,5
Hover over products below to view reaction partners
- Route of elimination
36% of an oral dose is eliminated as unchanged drug in the feces and 32% as the primary metabolite BZG791 in the feces. About 2% of an oral dose is eliminated in the urine as unchanged drug and 7.1% as the primary metabolite BZG791. In total 81% of an oral dose is eliminated in the feces and 14% is eliminated in the urine.7
- Half-life
The mean half life of alprelisib is 8 to 9 hours.7
- Clearance
The mean apparent oral clearance was 39.0L/h.4 The predicted clearance is 9.2L/hr under fed conditions.7
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Patients experiencing an overdose may present with hyperglycemia, nausea, asthenia, and rash. There is no antidote for an overdose of alpelisib so patients should be treated symptomatically.7
Data regarding an LD50 is not readily available.9 In clinical trials, patients were given doses of up to 450mg once daily.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Alpelisib can be increased when it is combined with Abametapir. Abatacept The metabolism of Alpelisib can be increased when combined with Abatacept. Abemaciclib The serum concentration of Alpelisib can be increased when it is combined with Abemaciclib. Abrocitinib The serum concentration of Abrocitinib can be decreased when it is combined with Alpelisib. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Alpelisib. - Food Interactions
- Exercise caution with St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of alpelisib.
- Take at the same time every day.
- Take with food. Food does not significantly affect the AUC of alpelisib.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Piqray Tablet, film coated 200 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU 
Piqray Tablet 200 mg/1 Oral Novartis Pharmaceuticals Corporation 2019-05-24 Not applicable US 
Piqray Tablet, film coated 150 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU Piqray Tablet 200 mg Oral Novartis 2020-06-29 Not applicable Canada 
Piqray Tablet, film coated 200 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Piqray Alpelisib (200 mg/1) + Alpelisib (50 mg/1) Kit; Tablet Oral Novartis Pharmaceuticals Corporation 2019-05-24 Not applicable US PIQRAY Alpelisib (200 MG) + Alpelisib (50 MG) Kit; Tablet, film coated Oral Novartis Europharm Limited 2020-12-05 Not applicable Italy 
PIQRAY Alpelisib (200 MG) + Alpelisib (50 MG) Kit; Tablet, film coated Oral Novartis Europharm Limited 2020-12-05 Not applicable Italy PIQRAY Alpelisib (200 MG) + Alpelisib (50 MG) Kit; Tablet, film coated Oral Novartis Europharm Limited 2020-12-05 Not applicable Italy Piqray Alpelisib (200 mg/1) + Alpelisib (50 mg/1) Kit; Tablet Oral Novartis Pharmaceuticals Corporation 2019-05-24 Not applicable US
Categories
- ATC Codes
- L01EM03 — Alpelisib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Breast Neoplasms
- Class I Phosphatidylinositol 3-Kinases, antagonists & inhibitors
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (moderate)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (moderate)
- Cytochrome P-450 CYP2C9 Inducers (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- Phosphatidylinositol 3-Kinases, antagonists & inhibitors
- Phosphatidylinositol-3-kinase (Pi3K) inhibitors
- Protein Kinase Inhibitors
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as proline and derivatives. These are compounds containing proline or a derivative thereof resulting from reaction of proline at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Proline and derivatives
- Alternative Parents
- Alpha amino acid amides / Pyrrolidinecarboxamides / 2,4,5-trisubstituted thiazoles / Pyridines and derivatives / Heteroaromatic compounds / Ureas / Primary carboxylic acid amides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds show 5 more
- Substituents
- 2,4,5-trisubstituted 1,3-thiazole / Alkyl fluoride / Alkyl halide / Alpha-amino acid amide / Aromatic heteromonocyclic compound / Azacycle / Azole / Carbonic acid derivative / Carbonyl group / Carboxamide group show 20 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 08W5N2C97Q
- CAS number
- 1217486-61-7
- InChI Key
- STUWGJZDJHPWGZ-LBPRGKRZSA-N
- 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
- IUPAC Name
- (2S)-N1-{4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl}pyrrolidine-1,2-dicarboxamide
- SMILES
- CC1=C(SC(NC(=O)N2CCC[C@H]2C(N)=O)=N1)C1=CC(=NC=C1)C(C)(C)C(F)(F)F
References
- General References
- Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Cadoo KA, Shapiro GI, Mayer EL, O'Cearbhaill RE, Coleman RL, Kochupurakkal B, Whalen C, Curtis J, Farooq S, Luo W, Eismann J, Buss MK, Aghajanian C, Mills GB, Palakurthi S, Kirschmeier P, Liu J, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA: Olaparib and alpha-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. Lancet Oncol. 2019 Apr;20(4):570-580. doi: 10.1016/S1470-2045(18)30905-7. Epub 2019 Mar 14. [Article]
- Rodon J, Curigliano G, Delord JP, Harb W, Azaro A, Han Y, Wilke C, Donnet V, Sellami D, Beck T: A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors. Oncotarget. 2018 Aug 3;9(60):31709-31718. doi: 10.18632/oncotarget.25854. eCollection 2018 Aug 3. [Article]
- Yang X, Zhang X, Huang M, Song K, Li X, Huang M, Meng L, Zhang J: New Insights into PI3K Inhibitor Design using X-ray Structures of PI3Kalpha Complexed with a Potent Lead Compound. Sci Rep. 2017 Nov 6;7(1):14572. doi: 10.1038/s41598-017-15260-5. [Article]
- James A, Blumenstein L, Glaenzel U, Jin Y, Demailly A, Jakab A, Hansen R, Hazell K, Mehta A, Trandafir L, Swart P: Absorption, distribution, metabolism, and excretion of [(14)C]BYL719 (alpelisib) in healthy male volunteers. Cancer Chemother Pharmacol. 2015 Oct;76(4):751-60. doi: 10.1007/s00280-015-2842-4. Epub 2015 Aug 8. [Article]
- James AD, Marvalin C, Luneau A, Meissner A, Camenisch G: Comparison of (19)F NMR and (14)C Measurements for the Assessment of ADME of BYL719 (Alpelisib) in Humans. Drug Metab Dispos. 2017 Aug;45(8):900-907. doi: 10.1124/dmd.117.075424. Epub 2017 May 31. [Article]
- De Buck SS, Jakab A, Boehm M, Bootle D, Juric D, Quadt C, Goggin TK: Population pharmacokinetics and pharmacodynamics of BYL719, a phosphoinositide 3-kinase antagonist, in adult patients with advanced solid malignancies. Br J Clin Pharmacol. 2014 Sep;78(3):543-55. doi: 10.1111/bcp.12378. [Article]
- FDA Approved Drug Products: PIQRAY (alpelisib) tablets, for oral use [Link]
- FDA Approved Drug Products: VIJOICE (alpelisib) tablets, for oral use [Link]
- Cayman Chemical: Alpelisib MSDS [Link]
- FDA Approved Drug Products: PIQRAY (alpelisib) tablets, for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0304878
- PubChem Compound
- 56649450
- PubChem Substance
- 347828332
- ChemSpider
- 28424123
- BindingDB
- 50436459
- 2169285
- ChEBI
- 93752
- ChEMBL
- CHEMBL2396661
- ZINC
- ZINC000068198368
- PDBe Ligand
- 1LT
- Wikipedia
- Phosphoinositide_3-kinase_inhibitor
- PDB Entries
- 4jps / 7myo / 7pg6 / 8gua / 8gub / 8gud / 8v8u / 8v8v
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Treatment Squamous Cell Cancers of the Head and Neck 1 somestatus stop reason just information to hide Not Available Available Not Available HR+, HER2-, Advanced Breast Cancer 1 somestatus stop reason just information to hide Not Available Available Not Available PIK3CA-Related Overgrowth Spectrum (PROS) 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available HR+ Advanced or Metastatic Breast Cancer 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available Lymphangioma 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit; tablet Oral Kit; tablet, film coated Oral Tablet Oral 150 mg/1 Tablet Oral 150 mg Tablet Oral 200 mg/1 Tablet Oral 200 mg Tablet Oral 50 mg Tablet Oral 500.000 mg Tablet, film coated Oral 200 mg Tablet, film coated Oral 150 mg Tablet, film coated Oral Granule Oral 50 mg/1 Tablet Oral 125 mg/1 Tablet Oral 50 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8227462 No 2012-07-24 2030-09-28 US US8476268 No 2013-07-02 2029-09-10 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00528 mg/mL ALOGPS logP 2.76 ALOGPS logP 2.81 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 7.79 Chemaxon pKa (Strongest Basic) 2.81 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 101.21 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 105.85 m3·mol-1 Chemaxon Polarizability 42.75 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0f96-0004900000-d9dc3aa20948b9a6341e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0ukc-0407900000-c01635164825876b9778 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-7504900000-aaff4ff6533307379394 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9210000000-e538b563b62bda8f215c Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05fs-9002000000-0918a6fd14b0f97edafe Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9023000000-9b674d4080056f5c6da1 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 191.60745 predictedDeepCCS 1.0 (2019) [M+H]+ 193.96547 predictedDeepCCS 1.0 (2019) [M+Na]+ 200.15466 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:23936502, PubMed:28676499). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, PubMed:28676499). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (PubMed:23936502, PubMed:28676499). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity)
- Specific Function
- 1-phosphatidylinositol-3-kinase activity
- Gene Name
- PIK3CA
- Uniprot ID
- P42336
- Uniprot Name
- Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
- Molecular Weight
- 124283.025 Da
References
- Chen IC, Hsiao LP, Huang IW, Yu HC, Yeh LC, Lin CH, Wei-Wu Chen T, Cheng AL, Lu YS: Phosphatidylinositol-3 Kinase Inhibitors, Buparlisib and Alpelisib, Sensitize Estrogen Receptor-positive Breast Cancer Cells to Tamoxifen. Sci Rep. 2017 Aug 29;7(1):9842. doi: 10.1038/s41598-017-10555-z. [Article]
- Yang X, Zhang X, Huang M, Song K, Li X, Huang M, Meng L, Zhang J: New Insights into PI3K Inhibitor Design using X-ray Structures of PI3Kalpha Complexed with a Potent Lead Compound. Sci Rep. 2017 Nov 6;7(1):14572. doi: 10.1038/s41598-017-15260-5. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- James AD, Marvalin C, Luneau A, Meissner A, Camenisch G: Comparison of (19)F NMR and (14)C Measurements for the Assessment of ADME of BYL719 (Alpelisib) in Humans. Drug Metab Dispos. 2017 Aug;45(8):900-907. doi: 10.1124/dmd.117.075424. Epub 2017 May 31. [Article]
- James A, Blumenstein L, Glaenzel U, Jin Y, Demailly A, Jakab A, Hansen R, Hazell K, Mehta A, Trandafir L, Swart P: Absorption, distribution, metabolism, and excretion of [(14)C]BYL719 (alpelisib) in healthy male volunteers. Cancer Chemother Pharmacol. 2015 Oct;76(4):751-60. doi: 10.1007/s00280-015-2842-4. Epub 2015 Aug 8. [Article]
- New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Rewcastle GW, Kolekar S, Buchanan CM, Gamage SA, Giddens AC, Tsang KY, Kendall JD, Singh R, Lee WJ, Smith GC, Han W, Matthews DJ, Denny WA, Shepherd PR, Jamieson SMF: Biological characterization of SN32976, a selective inhibitor of PI3K and mTOR with preferential activity to PI3Kalpha, in comparison to established pan PI3K inhibitors. Oncotarget. 2017 Jul 18;8(29):47725-47740. doi: 10.18632/oncotarget.17730. [Article]
- New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: PIQRAY (alpelisib) tablets, for oral use [Link]
Drug created at October 20, 2016 21:11 / Updated at October 05, 2024 06:30