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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 of PALBOCICLIB

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

Molecular Formula C24H29N7O2
Molecular Weight 447.5328
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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 TargetPharmacologyConditionPotency
11.0 nM [IC50]
4.0 nM [IC50]
5.0 nM [IC50]
15.0 nM [IC50]
9.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IBRANCE

Cmax

ValueDoseCo-administeredAnalytePopulation
104.1 ng/mL
125 mg single, oral
PALBOCICLIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
2483 ng × h/mL
125 mg single, oral
PALBOCICLIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
23.9 h
125 mg single, oral
PALBOCICLIB plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

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
Record UNII
G9ZF61LE7G
Record Status Validated (UNII)
Record Version