palbociclib   

GtoPdb Ligand ID: 7380

Synonyms: Ibrance® | PD-0332991 | PD0332991
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 [6-7,13]. This kinase inhibitor has anti-tumour activity in several tumour models [6-7,9,14-15].
The pharmaceutical formulation contains palbociclib isethionate (PubChem CID 11478676).
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2D Structure
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Physico-chemical Properties
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
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
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 [1,5,8,16]). 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
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, [3,10,17], 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].
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