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=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)

HIDE SMILES / InChI

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 10 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 8146	11.0 nM [IC50]
MDA-MB-175-VII 3 Target ID: CHEMBL1075497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578	Inhibitor 8146	4.0 nM [IC50]
ZR-75-30 3 Target ID: CHEMBL1075613 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578	Inhibitor 8146	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 8146	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 8146	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 8307	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 1.42292156E12

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) n = 3 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 3 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) n = 22 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 22 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) n = 3 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 3 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) n = 7 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 7 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 Co-administed with:: letrozole(2.5 mg/day) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	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: 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 Page: p. 112	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf Page: p. 112	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 Page: p. 112
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 Page: p. 112	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf Page: p. 112	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 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: https://pubmed.ncbi.nlm.nih.gov/22090362/	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: 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) n = 3 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 3 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) n = 7 Health Status: unhealthy Age Group: 54 years (range: 22–77 years) Sex: M+F Population Size: 7 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 Co-administed with:: letrozole(2.5 mg/day) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	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: 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 Co-administed with:: letrozole(2.5 mg/day) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	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: 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 Co-administed with:: letrozole(2.5 mg/day) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207103s000lbl.pdf	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: 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 Page: p. 112	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf Page: p. 112	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf Page: p. 112	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf Page: p. 112	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000MedR.pdf Page: p. 112

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670 inducer 753	inhibitor 1695	inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2B6 770 CYP2C8 869 CYP2C19 1410 CYP3A 208 CYP2A6 670 P-gp 1401 OAT3 625 OAT1 584 OCT2 630 OATP1B1 770 OATP1B3 691	SULT2A1 24 P-gp 1491 BCRP 545	CYP1A2 671 CYP2B6 521 CYP2C8 163

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2B6 946	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C8 923	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP3A 291	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
OAT1 588	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OAT3 627	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OATP1B1 785	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OATP1B3 700	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OCT2 631	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
P-gp 1588	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP3A 291	inhibitor 3185 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 545	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
P-gp 1491	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes
SULT2A1 24	substrate 3264 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 1603	inhibitor 1584 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
MolPort	MolPort-009-679-393	https://www.molport.com/shop/molecule-link/MolPort-009-679-393
ZINC	ZINC000003938686	http://zinc15.docking.org/substances/ZINC000003938686
eMolecules	32176408	https://www.emolecules.com/cgi-bin/more?vid=32176408

PubMed

Title	Date	PubMed
Primary care pediatrics vs. family practice: a nonissue.	1983 Aug	6885367
A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model.	2008 Jul 15	18632601
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
Advancing bioluminescence imaging technology for the evaluation of anticancer agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor models.	2009 Jan 1	19118051
Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts.	2010 Apr 15	20354191
Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure.	2010 Jul 15	20473330
Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM.	2010 Jun 22	20534551
Quantitative analysis of PD 0332991 in xenograft mouse tumor tissue by a 96-well supported liquid extraction format and liquid chromatography/mass spectrometry.	2010 Nov 2	20236782
Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.	2011 Mar 15	21278246
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 Jan 15	22090362
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.	2012 Jul 15	22767154
CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy.	2012 Jul 15	22751436
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.	2012 Oct 16	23079656
Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1.	2013 Jun 15	23676220
Palbociclib: first global approval.	2015 Apr	25792301
CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment.	2015 Mar 1	25501126

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).

Name

Type

Language

PALBOCICLIB

Official 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 [INN]

Common Name

English

PALBOCICLIB [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

WHO-ATC

L01XE33