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

Details

Stereochemistry ACHIRAL
Molecular Formula C24H29N7O2
Molecular Weight 447.5337
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PALBOCICLIB

SMILES

Cc1c2cnc(Nc3ccc(cn3)N4CCNCC4)nc2n(C5CCCC5)c(=O)c1C(=O)C

InChI

InChIKey=AHJRHEGDXFFMBM-UHFFFAOYSA-N
InChI=1S/C24H29N7O2/c1-15-19-14-27-24(28-20-8-7-18(13-26-20)30-11-9-25-10-12-30)29-22(19)31(17-5-3-4-6-17)23(33)21(15)16(2)32/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29)

HIDE SMILES / InChI

Molecular Formula C24H29N7O2
Molecular Weight 447.5337
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB09073

cancer as initial endocrine-based therapy for their metastatic disease.

Originator

Curator's Comment:: # Onyx Pharmaceuticals; Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
11 nM [IC50]
4 nM [IC50]
5 nM [IC50]
15 nM [IC50]
9 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IBRANCE

Approved Use

IBRANCE is indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival (PFS)

Launch Date

1422921600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
104.1 ng/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PALBOCICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2483 ng × h/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PALBOCICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
23.9 h
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PALBOCICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Sources:
125 mg 1 times / day steady, oral
MTD|RP2D
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3, 1 patient)
Sources:
150 mg 1 times / day steady, oral
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3-4, 2 patients)
Sources:
75 mg 1 times / day steady, oral
Dose: 75 mg, 1 times / day
Route: oral
Route: steady
Dose: 75 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3-4, 2 patients)
Sources:
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 63 years (range: 38 - 89 years)
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Sources:
Disc. AE: Neutropenia, Asthenia...
AEs leading to
discontinuation/dose reduction:
Neutropenia (6%)
Asthenia (1%)
Fatigue (1%)
Sources:
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, adult
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Dizziness (1 patient)
Sources:
250 mg 1 times / day multiple, oral
Overdose
Dose: 250 mg, 1 times / day
Route: oral
Route: multiple
Dose: 250 mg, 1 times / day
Sources:
unhealthy, adult
Disc. AE: Neutropenia...
AEs leading to
discontinuation/dose reduction:
Neutropenia (grade 4, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Neutropenia grade 3, 1 patient
DLT
125 mg 1 times / day steady, oral
MTD|RP2D
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Sources:
Neutropenia grade 3-4, 2 patients
DLT
150 mg 1 times / day steady, oral
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Sources:
Neutropenia grade 3-4, 2 patients
DLT
75 mg 1 times / day steady, oral
Dose: 75 mg, 1 times / day
Route: oral
Route: steady
Dose: 75 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Sources:
Asthenia 1%
Disc. AE
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 63 years (range: 38 - 89 years)
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Sources:
Fatigue 1%
Disc. AE
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 63 years (range: 38 - 89 years)
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Sources:
Neutropenia 6%
Disc. AE
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 63 years (range: 38 - 89 years)
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Sources:
Dizziness 1 patient
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, adult
Nausea 1 patient
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, adult
Vomiting 1 patient
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, adult
Neutropenia grade 4, 1 patient
Disc. AE
250 mg 1 times / day multiple, oral
Overdose
Dose: 250 mg, 1 times / day
Route: oral
Route: multiple
Dose: 250 mg, 1 times / day
Sources:
unhealthy, adult
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Targeting the cell division cycle in cancer: CDK and cell cycle checkpoint kinase inhibitors.
2005 Aug
A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6.
2006 Aug 1
Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase 4/6-dependent tumors and tissues.
2007 May 15
A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model.
2008 Jul 15
Treatment of growing teratoma syndrome.
2009 Jan 22
Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia.
2009 May 15
Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM.
2010 Jun 22
Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells.
2010 May
A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.
2011 Nov 15
Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis.
2011 Oct 21
p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells.
2012 Jul
CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy.
2012 Jul 15
Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy.
2012 Mar 21
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.
2012 May 17
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.
2012 Oct 16
The requirement for cyclin D function in tumor maintenance.
2012 Oct 16
Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma cells.
2013 Jan
A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.
2013 Jul
Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.
2013 Jun 1
MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged infant ALL.
2014
[Effect of PD0332991 on biological activity of hematopoietic stem cells in mice].
2014 Feb
Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines.
2014 Feb 17
CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers.
2014 Jul 15
Palbociclib: first global approval.
2015 Apr
Palbociclib Extends Survival in Advanced Breast Cancer.
2015 Jul
CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment.
2015 Mar 1
Patents

Sample Use Guides

IBRANCE capsules (Palbociclib) are taken orally with food in combination with letrozole. Recommended starting dose: 125 mg once daily taken with food for 21 days followed by 7 days off treatment
Route of Administration: Oral
Palbociclib (100 nM) significantly
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:32:37 UTC 2021
Edited
by admin
on Fri Jun 25 21:32:37 UTC 2021
Record UNII
G9ZF61LE7G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PALBOCICLIB
DASH   INN   USAN   WHO-DD  
INN   USAN  
Official Name English
PALBOCICLIB [MI]
Common Name English
6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-((5-(PIPERAZIN-1-YL)PYRIDIN-2-YL)AMINO)-8H-PYRIDO(2,3-D)PYRIMIDIN-7-ONE
Systematic Name English
IBRANCE
Brand Name English
PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE, 6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-((5-(1-PIPERAZINYL)-2-PYRIDINYL)AMINO)-
Systematic Name English
6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-((5-(PIPERAZIN-1-YL)PYRIDIN-2-YL)AMINO(PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE
Common Name English
PALBOCICLIB [USAN]
Common Name English
PALBOCICLIB [JAN]
Common Name English
PD-0332991
Code English
PALBOCICLIB [INN]
Common Name English
PALBOCICLIB [WHO-DD]
Common Name English
PALBOCICLIB [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC L01XE33
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
FDA ORPHAN DRUG 781420
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
NCI_THESAURUS C2185
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
NCI_THESAURUS C129825
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
NDF-RT N0000175605
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
Code System Code Type Description
FDA UNII
G9ZF61LE7G
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
MERCK INDEX
M11849
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
EVMPD
SUB177204
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
NDF-RT
N0000175082
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY Kinase Inhibitors [MoA]
NCI_THESAURUS
C49176
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL189963
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
NDF-RT
N0000190114
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
RXCUI
1601374
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY RxNorm
PUBCHEM
5330286
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
INN
9802
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
WIKIPEDIA
Palbociclib
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
LACTMED
Palbociclib
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
CAS
571190-30-2
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
DRUG CENTRAL
4941
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
DRUG BANK
DB09073
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
IUPHAR
7380
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
EXCRETED UNCHANGED
URINE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> NON-INDUCER
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
IC50
EXCRETED UNCHANGED
FECAL
TARGET -> INHIBITOR
IC50
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
log P CHEMICAL
Biological Half-life PHARMACOKINETIC
pKa CHEMICAL
pKa CHEMICAL
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

CSF/PLASMA RATIO PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
brain-to-plasma AUC ratios
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC