Identification

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Name
Alpelisib
Accession Number
DB12015
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Structure
Thumb
Synonyms
  • Alpelisib
External IDs
BYL 719 / BYL-719 / BYL719 / NVP-BYL719
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PiqrayTablet200 mg/1OralNovartis Pharmaceuticals Corporation2019-05-24Not applicableUs
PiqrayTablet150 mg/1OralNovartis Pharmaceuticals Corporation2019-05-24Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PiqrayAlpelisib (200 mg/1) + Alpelisib (50 mg/1)KitNovartis Pharmaceuticals Corporation2019-05-24Not applicableUs
PiqrayAlpelisib (200 mg/1) + Alpelisib (50 mg/1)KitNovartis Pharmaceuticals Corporation2019-05-24Not applicableUs
Categories
UNII
08W5N2C97Q
CAS number
1217486-61-7
Weight
Average: 441.47
Monoisotopic: 441.144630278
Chemical Formula
C19H22F3N5O2S
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

Pharmacology

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

Associated Conditions
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.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.Label

TargetActionsOrganism
APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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%.Label

Volume of distribution

The apparent volume of distribution at steady state is 114L.Label

Protein binding

Alpelisib is 89% protein bound.Label

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.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.Label Alpelisib can also be glucuronidated to form the M1 and M12 metabolites.4,5

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.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

Half life

The mean half life of alprelisib is 8 to 9 hours.Label

Clearance

The mean apparent oral clearance was 39.0L/h.4 The predicted clearance is 9.2L/hr under fed conditions.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

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Alpelisib.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Alpelisib.
AbemaciclibThe serum concentration of Alpelisib can be increased when it is combined with Abemaciclib.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Alpelisib.
AceclofenacThe serum concentration of Aceclofenac can be decreased when it is combined with Alpelisib.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Alpelisib.
AcetaminophenThe serum concentration of Alpelisib can be increased when it is combined with Acetaminophen.
AcetohexamideThe serum concentration of Acetohexamide can be decreased when it is combined with Alpelisib.
AcetyldigoxinAlpelisib may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be decreased when it is combined with Alpelisib.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. 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. [PubMed:30880072]
  2. 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. [PubMed:30167089]
  3. 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. [PubMed:29109464]
  4. 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. [PubMed:26254025]
  5. 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. [PubMed:28566285]
  6. 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. [PubMed:24617631]
  7. FDA Approved Drug Products: Alpelisib [Link]
External Links
PubChem Compound
56649450
PubChem Substance
347828332
ChemSpider
28424123
BindingDB
50436459
ChEBI
93752
ChEMBL
CHEMBL2396661
HET
1LT
Wikipedia
Phosphoinositide_3-kinase_inhibitor
PDB Entries
4jps
FDA label
Download (657 KB)
MSDS
Download (23.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdvanced Solid Tumors With an Alteration of the PIK3CA Gene / Estrogen Receptor Positive Breast Cancer1
1Active Not RecruitingTreatmentCancer of the Ovary / Cancer, Breast1
1Active Not RecruitingTreatmentCancer, Breast2
1Active Not RecruitingTreatmentHead and Neck Squamous Cell Cancer1
1Active Not RecruitingTreatmentHer2-Positive Breast Cancer / Recurrent Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
1Active Not RecruitingTreatmentLocoregionally Advanced / Squamous Cell Carcinoma of the Head and Neck (SCCHN)1
1Active Not RecruitingTreatmentMalignant Neoplasm of Pancreas1
1Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
1Active Not RecruitingTreatmentMetastatic or Locally-advanced Unresectable Breast Cancer1
1Active Not RecruitingTreatmentNeoplasms / Neoplasms, Breast / Neoplasms, Kidney / Pancreatic Neuroendocine Neoplasms1
1Active Not RecruitingTreatmentUveal Melanoma1
1CompletedBasic ScienceHepatic Impairment1
1CompletedTreatment3rd Line GIST1
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentAdvanced Solid Tumors / Metastatic Solid Tumors1
1CompletedTreatmentAdvanced and Selected Solid Tumors / Advanced and Selected Solid Tumors, AML, High Risk and Very High Risk MDS / High Risk and Very High Risk MDS / Leukemia Acute Myeloid Leukemia (AML)1
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentNeoplasms, Breast Neoplasms, Head and Neck Neoplasms1
1CompletedTreatmentPI3K Pathway Inhibition / Pre-menopausal Breast Cancer1
1CompletedTreatmentRelapsed and Refractory Multiple Myeloma1
1CompletedTreatmentSquamous Cell Carcinoma of Esophagus1
1CompletedTreatmentStomach Neoplasms Esophageal Neoplasms Metastatic Gastric Cancer Mutated PI3KCA Protein Overexpressed HER2 Protein / Stomach Neoplasms; Esophageal Neoplasms; Metastatic Gastric Cancer; Mutated PI3KCA Protein; Overexpressed HER2 Protein1
1Not Yet RecruitingTreatmentMalignant Neoplasm of Breast1
1Not Yet RecruitingTreatmentMeningiomas1
1RecruitingTreatmentAdvanced or Metastatic ER+ Breast Cancer1
1RecruitingTreatmentTumors, Solid1
1TerminatedTreatmentRectal Carcinoma1
1, 2Active Not RecruitingTreatmentCancer, Breast1
1, 2Active Not RecruitingTreatmentColorectal Cancers1
1, 2TerminatedTreatmentMetastatic Head and Neck Squamous Cell Carcinoma / Recurrent Head and Neck Squamous Cell Carcinoma / Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma / Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC) Patients Who Are Resistant or Ineligible/Intolerant to Platinum-based Chemotherapy1
1, 2TerminatedTreatmentPIK3CA Amplified Advanced Solid Tumors / PIK3CA Mutated Advanced Solid Tumors1
1, 2WithdrawnTreatmentNeoplasms, Oropharyngeal / Oropharyngeal Cancers / Squamous Carcinoma / Squamous Cell Carcinoma (SCC)1
2Active Not RecruitingTreatmentAdenocarcinoma Lung Cancer / Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma1
2CompletedTreatmentCancer, Breast1
2RecruitingPreventionHNSCC / Neoplasms, Head and Neck1
2RecruitingTreatmentBreast Cancer, PI3K, Alpelisib1
2RecruitingTreatmentCDKN2A-p16 Positive / Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma / Stage I Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7 / Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7 / Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7 / Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v71
2RecruitingTreatmentCancer, Breast1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentRecurrent or Metastatic Squamous Cell Carcinoma of Head and Neck1
3Active Not RecruitingTreatmentCancer, Breast1
Not AvailableAvailableNot AvailableHR+ Advanced or Metastatic Breast Cancer1
Not AvailableAvailableNot AvailableLymphangioma1
Not AvailableRecruitingTreatmentHead and Neck Squamous Cell Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit
TabletOral150 mg/1
TabletOral200 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00528 mg/mLALOGPS
logP2.76ALOGPS
logP2.81ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)7.79ChemAxon
pKa (Strongest Basic)2.81ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area101.21 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity105.85 m3·mol-1ChemAxon
Polarizability42.75 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Proline or derivatives / Alpha-amino acid amide / 2,4,5-trisubstituted 1,3-thiazole / Pyrrolidine carboxylic acid or derivatives / Pyrrolidine-2-carboxamide / Pyrrolidine-1-carboxamide / Pyridine / Azole / Heteroaromatic compound / Pyrrolidine
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate...
Gene Name
PIK3CA
Uniprot ID
P42336
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Molecular Weight
124283.025 Da
References
  1. 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. [PubMed:28852212]
  2. 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. [PubMed:29109464]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. [PubMed:28566285]
  2. 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. [PubMed:26254025]
  3. New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. 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. [PubMed:28537878]
  2. New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. New Mexico Cancer Alliance: Compassionate Use of Alpelisib [Link]

Drug created on October 20, 2016 15:11 / Updated on June 04, 2019 16:05