PALBOCICLIB ISETHIONATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H29N7O2.C2H6O4S
Molecular Weight	573.664
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OCCS(O)(=O)=O.CC(=O)C1=C(C)C2=CN=C(NC3=CC=C(C=N3)N4CCNCC4)N=C2N(C5CCCC5)C1=O

InChI

InChIKey=LYYVFHRFIJKPOV-UHFFFAOYSA-N

InChI=1S/C24H29N7O2.C2H6O4S/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;3-1-2-7(4,5)6/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29);3H,1-2H2,(H,4,5,6)

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 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 8297	11.0 nM [IC50]
MDA-MB-175-VII 3 Target ID: CHEMBL1075497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578	Inhibitor 8297	4.0 nM [IC50]
ZR-75-30 3 Target ID: CHEMBL1075613 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19874578	Inhibitor 8297	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 8297	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 8297	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 8429	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) 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 1737 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP3A 214 CYP2A6 707 P-gp 1461 OAT3 642 OAT1 599 OCT2 647 OATP1B1 788 OATP1B3 706	SULT2A1 24 P-gp 1537 BCRP 561	CYP1A2 701 CYP2B6 547 CYP2C8 168

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no [IC50 >30 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	no	PF-05089326 3
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=45 Page: 45.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP3A 298	inhibitor 3277 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 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207103Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes
SULT2A1 24	substrate 3367 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 1647	inhibitor 1626 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
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
Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts.	2010 Apr 15	20354191
[CDK4, a specific target in the treatment of lung adenocarcinomas mutated for KRAS].	2010 Dec	21187034
The landscape of somatic copy-number alteration across human cancers.	2010 Feb 18	20164920
A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.	2010 Jul 13	20609353
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
Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells.	2010 May	20100483
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
RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response.	2010 Oct 15	20948315
A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer.	2011 Apr 28	21217777
Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma.	2011 Jul 1	21593195
Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer.	2011 Jun	21367843
Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1).	2011 Jun 7	21610706
Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.	2011 Mar 15	21278246
A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.	2011 Nov 15	22094256
Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis.	2011 Oct 21	21880723
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
p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells.	2012 Jul	22711607
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
The CDK4/6 inhibitor PD0332991 reverses epithelial dysplasia associated with abnormal activation of the cyclin-CDK-Rb pathway.	2012 Jun	22508966
[(18)F]FLT-PET imaging does not always "light up" proliferating tumor cells.	2012 Mar 1	22170262
Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy.	2012 Mar 21	22302033
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.	2012 May 17	22383795
Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells.	2012 Oct	22869556
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.	2012 Oct 16	23079656
The requirement for cyclin D function in tumor maintenance.	2012 Oct 16	23079655
Attenuation of the retinoblastoma pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6.	2012 Sep 1	22761470
PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma.	2013	24098593
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 Aug	23898052
Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma cells.	2013 Jan	23138228
A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.	2013 Jul	23792647
Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.	2013 Jun 1	23569312
Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1.	2013 Jun 15	23676220
Targeting cell cycle and hormone receptor pathways in cancer.	2013 Nov 28	23708653
MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged infant ALL.	2014	24736461
[Effect of PD0332991 on biological activity of hematopoietic stem cells in mice].	2014 Feb	24606660
Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines.	2014 Feb 17	24549232
CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models.	2014 Jul	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 Jul	24495407
CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers.	2014 Jul 15	24986516
Palbociclib: first global approval.	2015 Apr	25792301
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 Jan	25524798
Palbociclib Extends Survival in Advanced Breast Cancer.	2015 Jul	26036642
Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.	2015 Jul 16	26030518
CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment.	2015 Mar 1	25501126
Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors.	2015 May 1	25522918

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 ISETHIONATE

Official Name

English

PD-0332991-0054

Code

English

Palbociclib isethionate [WHO-DD]

Common Name

English

PD-03329910054

Code

English

PALBOCICLIB ISETHIONATE [USAN]

Common Name

English

PD 0332991-0054

Code

English

PF-0008066573

Code

English

ETHANESULFONIC ACID, 2-HYDROXY-, COMPD. WITH 6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-((5-(1-PIPERAZINYL)-2-PYRIDINYL)AMINO)PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE (1:1)

Common 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 MONO(2-HYDROXYETHANESULFONATE)

Common Name

English

PF-00080665-73

Code

English

PALBOCICLIB ISETHIOLATE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2185