palbociclib   Click here for help

GtoPdb Ligand ID: 7380

Synonyms: Ibrance® | PD-0332991 | PD0332991
Approved drug PDB Ligand
palbociclib is an approved drug (FDA (2015), EMA (2016))
Compound class: Synthetic organic
Comment: Palbociclib is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6 [6-7,14]. This kinase inhibitor has anti-tumour activity in several tumour models [6-7,9,15-16].
The pharmaceutical formulation contains palbociclib isethionate (PubChem CID 11478676).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: palbociclib

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 105.04
Molecular weight 447.24
XLogP 3.29
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CC(=O)c1c(C)c2cnc(nc2n(c1=O)C1CCCC1)Nc1ccc(cn1)N1CCNCC1
Isomeric SMILES CC(=O)c1c(C)c2cnc(nc2n(c1=O)C1CCCC1)Nc1ccc(cn1)N1CCNCC1
InChI 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)
InChI Key AHJRHEGDXFFMBM-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
In August 2014 the drug's developer, Pfizer, announced the start of a multi-center, open-label expanded access program (EAP) in the United States. Through this program, palbociclib is being made available for use in combination with letrozole (an aromatase inhibitor) for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer for whom letrozole is considered appropriate therapy. This EAP is registered as clinical trial NCT02142868.

In February 2015 the US FDA approved palbociclib for the treatment of postmenopausal women with advanced (metastatic) breast cancer (in combination with letrozole as described above [1,5,8,17]). In early 2016, the FDA expanded use further by approving palbociclib in combination with fulvestrant (an estrogen receptor antagonist) for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy .

Palbociclib is being tested in many clinical trials to assess effectiveness against several other types of cancer. To view the current list of trials link to ClinicalTrials.gov.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The cyclin D-CDK4/6 (CDK-4/6:INK4:Rb) pathway is key to regulating cell growth in many types of human cancer [2,10-11], such as genetic subtypes of non-small cell lung cancer (NSCLC, [3,10,18], melanoma, Mantle cell lymphoma (MCL), and ovarian and breast cancers [3-4]. Inhibiting this pathway prevents cell cycle transition from G1 to S phase, induces cell senescence and in some cases results in apoptosis [3].
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)