Details
Stereochemistry | ACHIRAL |
Molecular Formula | C24H29N7O2 |
Molecular Weight | 447.5328 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(=O)C1=C(C)C2=CN=C(NC3=NC=C(C=C3)N4CCNCC4)N=C2N(C5CCCC5)C1=O
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)
Molecular Formula | C24H29N7O2 |
Molecular Weight | 447.5328 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB09073
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB09073
Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6 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. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein. Inhibition of these proteins leads to reduced phosphorylation of Rb, inhibition of downstream signalling, and increased tumor growth arrest. Palbociclib received an accelerated approval from the Food and Drug Administration on February 3, 2015. Palbociclib is marketed under the trade name Ibrance. IBRANCE is a kinase inhibitor 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.
Originator
Sources: http://adisinsight.springer.com/drugs/800020668
Curator's Comment: # Onyx Pharmaceuticals; Pfizer
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
11.0 nM [IC50] | |||
Target ID: CHEMBL1075497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578 |
4.0 nM [IC50] | ||
Target ID: CHEMBL1075613 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578 |
5.0 nM [IC50] | ||
15.0 nM [IC50] | |||
9.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | IBRANCE Approved UseIBRANCE 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 Date2015 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
104.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26991823 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2483 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26991823 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
23.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26991823 |
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
Dose | Population | Adverse 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) n = 3 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 3 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) n = 22 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 22 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) n = 3 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 3 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) n = 7 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 7 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 Co-administed with:: letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years (range: 38 - 89 years) n = 83 Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Population Size: 83 Sources: |
Disc. AE: Neutropenia, Asthenia... AEs leading to discontinuation/dose reduction: Neutropenia (6%) Sources: Asthenia (1%) Fatigue (1%) |
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: Page: p. 112 |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: Page: p. 112 |
Other AEs: Nausea, Vomiting... Other AEs: Nausea (1 patient) Sources: Page: p. 112Vomiting (1 patient) Dizziness (1 patient) |
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: Page: p. 112 |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: Page: p. 112 |
Disc. AE: Neutropenia... AEs leading to discontinuation/dose reduction: Neutropenia (grade 4, 1 patient) Sources: Page: p. 112 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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) n = 22 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 22 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) n = 3 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 3 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) n = 7 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 7 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 Co-administed with:: letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years (range: 38 - 89 years) n = 83 Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Population Size: 83 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 Co-administed with:: letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years (range: 38 - 89 years) n = 83 Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Population Size: 83 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 Co-administed with:: letrozole(2.5 mg/day) Sources: |
unhealthy, 63 years (range: 38 - 89 years) n = 83 Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Population Size: 83 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: Page: p. 112 |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: Page: p. 112 |
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: Page: p. 112 |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: Page: p. 112 |
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: Page: p. 112 |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: Page: p. 112 |
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: Page: p. 112 |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: Page: p. 112 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000PharmR.pdf#page=71 Page: 71.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Primary care pediatrics vs. family practice: a nonissue. | 1983 Aug |
|
The landscape of somatic copy-number alteration across human cancers. | 2010 Feb 18 |
|
Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells. | 2010 May |
|
RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response. | 2010 Oct 15 |
|
A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer. | 2011 Apr 28 |
|
Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma. | 2011 Jul 1 |
|
p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. | 2012 Jul |
|
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia. | 2012 Oct 16 |
|
Attenuation of the retinoblastoma pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6. | 2012 Sep 1 |
|
Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1. | 2013 Jun 15 |
|
Targeting cell cycle and hormone receptor pathways in cancer. | 2013 Nov 28 |
|
Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines. | 2014 Feb 17 |
|
CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models. | 2014 Jul |
|
Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines. | 2014 Jul |
|
CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. | 2014 Jul 15 |
|
Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. | 2015 Jul 16 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578
Palbociclib (100 nM) significantly
blocks phoshorylation of pRb (phospho-Rb) at serine 780 in sensitive human breast cancer cell lines (IC50 < 150 nM).
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 19:38:50 GMT 2023
by
admin
on
Fri Dec 15 19:38:50 GMT 2023
|
Record UNII |
G9ZF61LE7G
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Brand Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
WHO-ATC |
L01XE33
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
||
|
FDA ORPHAN DRUG |
781420
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
||
|
NCI_THESAURUS |
C2185
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
||
|
NCI_THESAURUS |
C129825
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
||
|
NDF-RT |
N0000175605
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
G9ZF61LE7G
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
m11849
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
SUB177204
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
85993
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
N0000175082
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | Kinase Inhibitors [MoA] | ||
|
DTXSID40972590
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
C49176
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
CHEMBL189963
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
N0000190114
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | Cytochrome P450 3A Inhibitors [MoA] | ||
|
1601374
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | RxNorm | ||
|
ZZ-152
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
100000163078
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
5330286
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
G9ZF61LE7G
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
9802
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
Palbociclib
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
Palbociclib
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
571190-30-2
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
4941
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
DB09073
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
PRIMARY | |||
|
7380
Created by
admin on Fri Dec 15 19:38:50 GMT 2023 , Edited by admin on Fri Dec 15 19:38:50 GMT 2023
|
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 |
|
||
|
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 PHARMACOKINETIC PHARMACOKINETIC |
|
||
Volume of Distribution | PHARMACOKINETIC |
|
|
|||