PALBOCICLIB

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

Structure Search

SMILES

CC(=O)C1=C(C)C2=C(N=C(NC3=CC=C(C=N3)N4CCNCC4)N=C2)N(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)

HIDE SMILES / InChI

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/15542782
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 4/cyclin D1 11 Target ID: CHEMBL1907601 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/26995305 \| https://www.ncbi.nlm.nih.gov/pubmed/15542782	Inhibitor 8504	11.0 nM [IC50]
MDA-MB-175-VII 3 Target ID: CHEMBL1075497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578	Inhibitor 8504	4.0 nM [IC50]
ZR-75-30 3 Target ID: CHEMBL1075613 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578	Inhibitor 8504	5.0 nM [IC50]
CDK6/cyclin D2 3 Target ID: CHEMBL3301386 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/26995305 \| https://www.ncbi.nlm.nih.gov/pubmed/15542782	Inhibitor 8504	15.0 nM [IC50]
CDK4/Cyclin D3 3 Target ID: CHEMBL3038472 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/26995305 \| https://www.ncbi.nlm.nih.gov/pubmed/15542782	Inhibitor 8504	9.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	Primary		Approved 8583	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 2015

C_max

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

T_1/2

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: https://pubmed.ncbi.nlm.nih.gov/22090362/	unhealthy, 54 years (range: 22–77 years) Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/	Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/
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: https://pubmed.ncbi.nlm.nih.gov/22090362/	unhealthy, 54 years (range: 22–77 years) Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/
150 mg 1 times / day steady, oral Dose: 150 mg, 1 times / day Route: oral Route: steady Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/	unhealthy, 54 years (range: 22–77 years) Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3-4, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/
75 mg 1 times / day steady, oral Dose: 75 mg, 1 times / day Route: oral Route: steady Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/	unhealthy, 54 years (range: 22–77 years) Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3-4, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	unhealthy, 63 years (range: 38 - 89 years) Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	Disc. AE: Neutropenia, Asthenia... AEs leading to discontinuation/dose reduction: Neutropenia (6%) Asthenia (1%) Fatigue (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	Other AEs: Nausea, Vomiting... Other AEs: Nausea (1 patient) Vomiting (1 patient) Dizziness (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	Disc. AE: Neutropenia... AEs leading to discontinuation/dose reduction: Neutropenia (grade 4, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf

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: https://pubmed.ncbi.nlm.nih.gov/22090362/	unhealthy, 54 years (range: 22–77 years) Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/
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: https://pubmed.ncbi.nlm.nih.gov/22090362/	unhealthy, 54 years (range: 22–77 years) Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/
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: https://pubmed.ncbi.nlm.nih.gov/22090362/	unhealthy, 54 years (range: 22–77 years) Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22090362/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	unhealthy, 63 years (range: 38 - 89 years) Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	unhealthy, 63 years (range: 38 - 89 years) Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	unhealthy, 63 years (range: 38 - 89 years) Health Status: unhealthy Age Group: 63 years (range: 38 - 89 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP3A 227 CYP2A6 879 P-gp 1741 OAT3 747 OAT1 725 OCT2 779 OATP1B1 1079 OATP1B3 961	SULT2A1 28 P-gp 2052 BCRP 697	CYP1A2 832 CYP2B6 669 CYP2C8 198

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	weak

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes
SULT2A1 28	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000PharmR.pdf#page=71 Page: 71.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85993	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85993
ChemicalBook	CB62464897	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62464897
eMolecules	32176408	https://www.emolecules.com/cgi-bin/more?vid=32176408
MolPort	MolPort-009-679-393	https://www.molport.com/shop/molecule-link/MolPort-009-679-393
ZINC	ZINC000003938686	http://zinc15.docking.org/substances/ZINC000003938686

PubMed

Title	Date	PubMed
Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.	2015-07-16	26030518
Palbociclib Extends Survival in Advanced Breast Cancer.	2015-07	26036642
Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors.	2015-05-01	25522918
Palbociclib: first global approval.	2015-04	25792301
CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment.	2015-03-01	25501126
The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.	2015-01	25524798
CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers.	2014-07-15	24986516
CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models.	2014-07	25221644
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.	2014-07	24495407
Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines.	2014-02-17	24549232
[Effect of PD0332991 on biological activity of hematopoietic stem cells in mice].	2014-02	24606660
MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged infant ALL.	2014	24736461
Targeting cell cycle and hormone receptor pathways in cancer.	2013-11-28	23708653
PD-0332991, a potent and selective inhibitor of cyclin-dependent kinase 4/6, demonstrates inhibition of proliferation in renal cell carcinoma at nanomolar concentrations and molecular markers predict for sensitivity.	2013-08	23898052
A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.	2013-07	23792647
Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1.	2013-06-15	23676220
Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.	2013-06-01	23569312
Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma cells.	2013-01	23138228
PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma.	2013	24098593
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.	2012-10-16	23079656
The requirement for cyclin D function in tumor maintenance.	2012-10-16	23079655
Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells.	2012-10	22869556
Attenuation of the retinoblastoma pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6.	2012-09-01	22761470
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.	2012-07-15	22767154
CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy.	2012-07-15	22751436
p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells.	2012-07	22711607
The CDK4/6 inhibitor PD0332991 reverses epithelial dysplasia associated with abnormal activation of the cyclin-CDK-Rb pathway.	2012-06	22508966
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.	2012-05-17	22383795
Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy.	2012-03-21	22302033
[(18)F]FLT-PET imaging does not always "light up" proliferating tumor cells.	2012-03-01	22170262
Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer.	2012-01-15	22090362
A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.	2011-11-15	22094256
Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis.	2011-10-21	21880723
Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma.	2011-07-01	21593195
Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1).	2011-06-07	21610706
Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer.	2011-06	21367843
A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer.	2011-04-28	21217777
Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.	2011-03-15	21278246
[CDK4, a specific target in the treatment of lung adenocarcinomas mutated for KRAS].	2010-12	21187034
Quantitative analysis of PD 0332991 in xenograft mouse tumor tissue by a 96-well supported liquid extraction format and liquid chromatography/mass spectrometry.	2010-11-02	20236782
RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response.	2010-10-15	20948315
Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure.	2010-07-15	20473330
A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.	2010-07-13	20609353
Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM.	2010-06-22	20534551
Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells.	2010-05	20100483
Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts.	2010-04-15	20354191
The landscape of somatic copy-number alteration across human cancers.	2010-02-18	20164920
CDK inhibitors as potential breast cancer therapeutics: new evidence for enhanced efficacy in ER+ disease.	2009	20067604
PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro.	2009	19874578
Primary care pediatrics vs. family practice: a nonissue.	1983-08	6885367

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Mon Mar 31 19:51:59 GMT 2025` Edited by `admin` on `Mon Mar 31 19:51:59 GMT 2025`
Record UNII	G9ZF61LE7G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PALBOCICLIB

Official Name

English

palbociclib [INN]

Preferred Name

English

Palbociclib [WHO-DD]

Common 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 [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

WHO-ATC

L01XE33