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
Bioactivity Comments
Palbociclib acts via inhibition of CDK4/6 to dose-dependently reduce phosphorylation of the retinoblastoma protein (Rb) with an IC50 of 30nM [14] in both MV4-11 and MOLM13 acute myelocytic leukemia (AML) cell lines.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
cyclin dependent kinase 4 Hs Inhibitor Inhibition 7.4 – 8.0 pIC50 - 7,12
pIC50 8.0 (IC50 1.1x10-8 M) [7]
pIC50 7.4 (IC50 4.4x10-8 M) [12]
cyclin dependent kinase 6 Hs Inhibitor Inhibition 7.4 – 7.8 pIC50 - 7,12
pIC50 7.8 (IC50 1.6x10-8 M) [7]
pIC50 7.4 (IC50 3.6x10-8 M) [12]
Ligand mentioned in the following text fields