U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H22F3N5O2S
Molecular Weight 441.47
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALPELISIB

SMILES

CC1=C(SC(NC(=O)N2CCC[C@H]2C(N)=O)=N1)C3=CC=NC(=C3)C(C)(C)C(F)(F)F

InChI

InChIKey=STUWGJZDJHPWGZ-LBPRGKRZSA-N
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

HIDE SMILES / InChI
Molecular Formula C19H22F3N5O2S
Molecular Weight 441.47
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Alpelisib (BYL719) is a PI3Kα-selective inhibitor. PI3K-AKT-mTOR pathway is frequently activated in cancer, therefore investigational PI3K inhibitor alpelisib is considered to be effective as an anticancer agent and has been in clinical development by Novartis. Alpelisib have demonstrated activity in preclinical models of solid tumors and had favorable tolerability profiles, with the most common adverse events consistent with “on-target” inhibition of PI3K in early clinical studies. There are ongoing clinical trials of alpelisib in a range of cancer types, including breast cancer, head and neck squamous cell carcinoma, non-small cell lung carcinoma, lymphoma, and glioblastoma multiforme. Combination therapy with other chemo therapeutics may be preferable.

Originator

Approval Year

2019
334
Targets

Targets

Primary TargetPharmacologyConditionPotency
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
9
Target ID: P42336
Gene ID: 5290.0
Gene Symbol: PIK3CA
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 5.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2480 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212526s000lbl.pdf
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ALPELISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
33224 ng × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212526s000lbl.pdf
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ALPELISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.5 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212526s000lbl.pdf
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ALPELISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
11%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212526s000lbl.pdf
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ALPELISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
400 mg 1 times / day steady, oral
Studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
unhealthy, 48.0 years (range: 24-72 years)
n = 7
Health Status: unhealthy
Age Group: 48.0 years (range: 24-72 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
DLT: Maculopapular rash, Conjunctivitis...
Dose limiting toxicities:
Maculopapular rash (grade 3, 2 patients)
Conjunctivitis (grade 2, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
350 mg 1 times / day steady, oral
Studied dose
Dose: 350 mg, 1 times / day
Route: oral
Route: steady
Dose: 350 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
unhealthy, 54.5 years (range: 31-72 years)
n = 8
Health Status: unhealthy
Age Group: 54.5 years (range: 31-72 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
DLT: Tumor infection...
Dose limiting toxicities:
Tumor infection (grade 4, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Disc. AE: Hyperglycemia, Rash...
AEs leading to
discontinuation/dose reduction:
Hyperglycemia (grade 3-4, 4.2%)
Rash (grade 3-4, 1.1%)
Diarrhea (grade 3-4, 0.4%)
Fatigue (grade 3-4, 1.1%)
Nausea (grade 3-4, 0.4%)
Hyperglycaemia (grade 3-4, 31.3%)
Diarrhoea (grade 3-4, 5.6%)
Rash (grade 3-4, 9.2%)
Rash maculo-papular (grade 3-4, 8.8%)
Stomatitis (grade 3-4, 2.1%)
Mucosal inflammation (grade 3-4, 1.4%)
Nausea (grade 3-4, 1.4%)
Lipase increased (grade 3-4, 3.5%)
Pyrexia (grade 3-4, 0.7%)
Fatigue (grade 3-4, 1.4%)
Pruritus (grade 3-4, 0.4%)
Vomiting (grade 3-4, 0.4%)
Asthenia (grade 3-4, 1.1%)
Decreased appetite (grade 3-4, 0.4%)
Alanine aminotransferase increased (grade 3-4, 2.1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
450 mg 1 times / day steady, oral
Highest studied dose
Dose: 450 mg, 1 times / day
Route: oral
Route: steady
Dose: 450 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 68
unhealthy
Health Status: unhealthy
Condition: advanced solid malignancies
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 68
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 68
400 mg 1 times / day steady, oral
MTD
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 76, 87
unhealthy
n = 33
Health Status: unhealthy
Condition: advanced solid malignancies
Population Size: 33
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 76, 87
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 76, 87
AEs

AEs

AESignificanceDosePopulation
Conjunctivitis grade 2, 1 patient
DLT
400 mg 1 times / day steady, oral
Studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
unhealthy, 48.0 years (range: 24-72 years)
n = 7
Health Status: unhealthy
Age Group: 48.0 years (range: 24-72 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
Maculopapular rash grade 3, 2 patients
DLT
400 mg 1 times / day steady, oral
Studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
unhealthy, 48.0 years (range: 24-72 years)
n = 7
Health Status: unhealthy
Age Group: 48.0 years (range: 24-72 years)
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
Tumor infection grade 4, 1 patient
DLT
350 mg 1 times / day steady, oral
Studied dose
Dose: 350 mg, 1 times / day
Route: oral
Route: steady
Dose: 350 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
unhealthy, 54.5 years (range: 31-72 years)
n = 8
Health Status: unhealthy
Age Group: 54.5 years (range: 31-72 years)
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/30588709
Decreased appetite grade 3-4, 0.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Diarrhea grade 3-4, 0.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Nausea grade 3-4, 0.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Pruritus grade 3-4, 0.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Vomiting grade 3-4, 0.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Pyrexia grade 3-4, 0.7%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Asthenia grade 3-4, 1.1%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Fatigue grade 3-4, 1.1%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Rash grade 3-4, 1.1%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Fatigue grade 3-4, 1.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Mucosal inflammation grade 3-4, 1.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Nausea grade 3-4, 1.4%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Alanine aminotransferase increased grade 3-4, 2.1%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Stomatitis grade 3-4, 2.1%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Lipase increased grade 3-4, 3.5%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Hyperglycaemia grade 3-4, 31.3%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Hyperglycemia grade 3-4, 4.2%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Diarrhoea grade 3-4, 5.6%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Rash maculo-papular grade 3-4, 8.8%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Rash grade 3-4, 9.2%
Disc. AE
300 mg 1 times / day steady, oral
Recommended
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Co-administed with::
fulvestrant(500 mg was administered intramuscularly on Cycle 1, Day 1 and 15 and then at Day 1 of each 28-day cycle during treatment phase)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
unhealthy, 63 years (range: 25 - 92 years)
n = 284
Health Status: unhealthy
Age Group: 63 years (range: 25 - 92 years)
Sex: M+F
Population Size: 284
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212526Orig1s000MultidisciplineR.pdf
Page: p. 138
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587
inducer
389
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461

sulfotransferases
1

BSEP
402

OATP1B1
788

OATP1B3
706

OCT1
512

OAT3
642

MATE1
306

MATE2
263

BCRP
699

OAT1
599
BCRP
561
CYP2B6
547

CYP3A
129

CYP2C8
168
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OAT3
644
 low [Ki 1.38 uM]
BZG791
1
CYP2B6
1001
 no [EC50 26 uM]
BZG791
1
CYP2C9
1819
 no [EC50 34 uM]
BZG791
1
CYP2C8
965
 no [EC50 66 uM]
BZG791
1
MATE1
308
 no [Ki 101.5 uM]
OAT1
603
 no [Ki 139.6 uM]
BZG791
1
OCT1
543
 no [Ki 190.8 uM]
BZG791
1
OATP1B1
803
 no [Ki 20.9 uM]
MATE1
308
 no [Ki 215.5 uM]
BZG791
1
OAT3
644
 no [Ki 29.4 uM]
sulfotransferases
1
 no [Ki 36 uM]
OATP1B3
715
 no [Ki 40 uM]
OATP1B3
715
 no [Ki 42.4 uM]
BZG791
1
BSEP
403
 no [Ki 49.6 uM]
BZG791
1
BSEP
403
 no [Ki 74.5 uM]
BCRP
773
 no [Ki 77.6 uM]
BZG791
1
OATP1B1
803
 no [Ki 8.59 uM]
BZG791
1
OCT1
543
 no [Ki 91.6 uM]
MATE2
263
 no [Ki >175 uM]
CYP2C9
1819
 yes [EC50 2.2 uM]
CYP2B6
1001
 yes [EC50 3 uM]
P-gp
1650
 yes [Ki 96.7 uM]
CYP3A
298
 yes
CYP3A4
1925
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
561
 yes [Km 2 uM]
CYP3A4
1737
 yes [Km 24.95 uM]
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
hERG
1647
BZG791
1
Sourcing

Sourcing

Vendor/AggregatorIDURL
AA Blocks
AA0015MQ
https://www.aablocks.com/goods/Goods/detail?id=AA0015MQ
AK Scientific, Inc. (AKSCI)
2294AH
http://www.aksci.com/item_detail.php?cat=2294AH
Aaron Chemicals
AR0016EI
http://www.aaronchem.com/1217486-61-7
AbMole Bioscience
M2104
http://www.abmole.com/products/byl719.html
Acadechem
ACDS-067976
http://www.acadechemical.com/product/142675
Achemtek
0104-035819
http://www.achemtek.com/1217486-61-7
Adooq BioScience
A11328
https://www.adooq.com/byl719.html
Alsachim
4528
http://www.alsachim.com/product-C5869-glo.bal-view.html
Ambeed
A130937
https://www.ambeed.com/products/1217486-61-7.html
Angene
AGN-PC-0WA1WV
http://www.angenechemical.com/productshow/AGN-PC-0WA1WV.html
ApexBio Technology
A8346
http://www.apexbt.com/byl-719.html
Aurum Pharmatech LLC
W-5917
http://www.Aurumpharmatech.com/Product/ProductDetails/W_5917
Axon MedChem
2925
https://www.axonmedchem.com/product/2925
BioCrick
BCC3707
http://www.biocrick.com/BYL-719-BCC3707.html
BioSynth
J-004627
https://www.biosynth.com/en/products/all-products/products/J-004627.html
Boerchem
BC600512
http://www.boerchem.com/?product_43347.html
CSNpharm
CSN13709
https://www.csnpharm.com/products/alpelisib.html
Chem Scene
CS-0663
http://www.chemscene.com/1217486-61-7.html
Chemspace
CSSB00015188197
https://chem-space.com/CSSB00015188197
Excenen
EX-A405
http://www.excenen.com/searchresultlist.php?id=1217486-61-7
Lab Network
LN01288613
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01288613
Matrix Scientific
120551
https://www.matrixscientific.com/120551.html
MedChem Express
cas:1217486-61-7;BYL-719
http://www.medchemexpress.com/product/BYL-719.html
MedChem Express
HY-15244
https://www.medchemexpress.com/BYL-719.html
Selleck Chemicals
S2814
http://www.selleckchem.com/products/byl719.html
Sinfoo Biotech
S052319
http://www.sinfoobiotech.com/product/1055717
Smolecule
S548345
http://www.smolecule.com/products/s548345
Synblock Inc
SB16575
http://www.synblock.com/product/1217486-61-7.html
THE BioTek
bt-287756
https://www.thebiotek.com/product/inhibitors/bt-287756
VladaChem
VL260030-100MG
https://www.vladachem.com/product.php?products=1217486-61-7
Yuhao Chemical
RT4239
http://www.chemyuhao.com/1217486-61-7.html
abcr GmbH
AB337610
http://www.abcr.com/shop/en/AB337610
eNovation Chemicals
D501882
http://www.enovationchem.com/productDetails.asp?productID=D501882
eNovation Chemicals
Y0975492
https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0975492
PubMed

PubMed

TitleDatePubMed
Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation.
2013 Jul 1
Absorption, distribution, metabolism, and excretion of [(14)C]BYL719 (alpelisib) in healthy male volunteers.
2015 Oct
PI3K inhibitors as new cancer therapeutics: implications for clinical trial design.
2016
Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treatment order.
2016 Jan
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer.
2017 Jan 1
Patents

Patents

20100105711
1
20120263712
1
20140023661
1
20140171470
1

Sample Use Guides

In Vivo Use Guide
Alpelisib (300 mg once daily) in combination with fulvestrant (500 mg; intramuscular injection on day 1 and day 15 of cycle 1, and then day 1 of each subsequent 28-day cycle) for men and postmenopausal women with hormone receptor positive, HER2-negative advanced breast cancer which progressed on or after aromatase inhibitor treatment.
Route of Administration: Oral
In Vitro Use Guide
Overexpression of FGFR1 in ER+/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro .
Substance Class Chemical
Created
by admin
on Sat Dec 16 06:49:18 GMT 2023
Edited
by admin
on Sat Dec 16 06:49:18 GMT 2023
Record UNII
08W5N2C97Q
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALPELISIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
(2S)-N1-{4-Methyl-5-[1-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl}pyrrolidine-1,2-dicarboxamide
Systematic Name English
VIJOICE
Brand Name English
NVP-BYL719
Code English
ALPELISIB [ORANGE BOOK]
Common Name English
ALPELISIB [MI]
Common Name English
BYL719
Code English
ALPELISIB [JAN]
Common Name English
Alpelisib [WHO-DD]
Common Name English
alpelisib [INN]
Common Name English
1,2-PYRROLIDINEDICARBOXAMIDE, N1-(4-METHYL-5-(2-(2,2,2-TRIFLUORO-1,1-DIMETHYLETHYL)-4-PYRIDINYL)-2-THIAZOLYL)-, (2S)-
Systematic Name English
PIQRAY
Brand Name English
ALPELISIB [USAN]
Common Name English
BYL-719
Common Name English
(S)-PYRROLIDINE-1,2-DICARBOXYLIC ACID 2-AMIDE 1-(4-METHYL-5-(2-(2,2,2-TRIFLUORO-1,1-DIMETHYLETHYL)-PYRIDIN-4-YL)THIAZOL-2-YL)AMIDE
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 930022
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
FDA ORPHAN DRUG 710819
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
NCI_THESAURUS C2152
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
Code System Code Type Description
USAN
EF-18
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
RXCUI
2169285
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
DRUG BANK
DB12015
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
SMS_ID
100000166553
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
WIKIPEDIA
Alpelisib
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
PUBCHEM
56649450
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
DRUG CENTRAL
5328
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
EPA CompTox
DTXSID70153355
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
MERCK INDEX
m12147
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
NCI_THESAURUS
C94214
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
INN
9833
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
EVMPD
SUB180707
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
DAILYMED
08W5N2C97Q
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
ChEMBL
CHEMBL2396661
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
CAS
1217486-61-7
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
FDA UNII
08W5N2C97Q
Created by admin on Sat Dec 16 06:49:19 GMT 2023 , Edited by admin on Sat Dec 16 06:49:19 GMT 2023
PRIMARY
Related Record Type Details
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
The in vitro study result indicated that alpelisib is a weak P-gp inhibitor with a Ki of 98.6 μM (R0900459).
Ki
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT ALPHA ISOFORM
TARGET -> INHIBITOR
IC50
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT DELTA ISOFORM
TARGET -> INHIBITOR
IC50
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT GAMMA ISOFORM
TARGET -> INHIBITOR
IC50
ADENOSINE RECEPTOR A3
OFF-TARGET->INHIBITOR
IC50
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT BETA ISOFORM
TARGET -> INHIBITOR
IC50
ADENOSINE RECEPTOR A1
OFF-TARGET->INHIBITOR
IC50
Structure of ALPELISIB
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
In vitro, protein binding of alpelisib is 89% and is independent of concentration.
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> SUBSTRATE
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Structure of ALPELISIB
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
In vitro, alpelisib is a strong time-dependent inhibitor of CYP3A4.
TIME-DEPENDENT INHIBITION
Ki
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INDUCER
STRONG
Related Record Type Details
Structure of ALPELISIB ACID
METABOLITE -> PARENT
MAJOR
FECAL; PLASMA; URINE
Related Record Type Details
Structure of ALPELISIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
blood-to-plasma ratio PHARMACOKINETIC
NIH
NCATS
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DISCLAIMER
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