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

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

Molecular Formula	C2H6O4S
Molecular Weight	126.132
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 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
Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts.	2004 Nov	15542782
Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6.	2005 Apr 7	15801831
Targeting the cell division cycle in cancer: CDK and cell cycle checkpoint kinase inhibitors.	2005 Aug	15964238
A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6.	2006 Aug 1	16885367
Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition.	2006 Jun 29	16789739
Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells.	2006 May	16731763
Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity.	2006 Sep 1	16690963
Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase 4/6-dependent tumors and tissues.	2007 May 15	17510401
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
Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells.	2009 Mar 19	19060242
Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia.	2009 May 15	19435910
[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
Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells.	2010 May	20100483
A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.	2011 Nov 15	22094256
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
The CDK4/6 inhibitor PD0332991 reverses epithelial dysplasia associated with abnormal activation of the cyclin-CDK-Rb pathway.	2012 Jun	22508966
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.	2012 May 17	22383795
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
Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.	2013 Jun 1	23569312
Targeting cell cycle and hormone receptor pathways in cancer.	2013 Nov 28	23708653
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 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

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 `Fri Dec 16 18:42:19 UTC 2022` Edited by `admin` on `Fri Dec 16 18:42:19 UTC 2022`
Record UNII	W1NYL2IRDR
Record Status	`Validated (UNII)`
Record Version

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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