compound 9 [Lin et al., 2023]   Click here for help

GtoPdb Ligand ID: 12806

Compound class: Synthetic organic
Comment: This compound is reported to exhibit dual functions as a poly ADP-ribose polymerase 1 (PARP1) inhibitor and cyclin-dependent kinase 12 (CDK12) inhibitor [1]. These two enzymes are important components of the DNA damage repair (DDR) response. CDK12 may be overexpressed in aggressive HER2-positive breast cancers. PARP inhibition is an established mechanism that is employed to disrupt DDR in cancer cells, particulary those with existing defects in homologous recombination such as BRCA-mutated breast cancers. Compound 9 was developed to investigate the anti-tumour potential of simultaneous disruption of the activities of these two molecular targets. It acts is a direct inhibitor of PARP1 and reduces expression of CDK12.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 98.96
Molecular weight 556.63
XLogP 1.08
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES C1CCN(CC1)CCCOC2=NC3=C(C=N2)CN(CC3)C(=O)C4=CC(=CC=C4F)CC5=NNC(=O)C6=C5C=CC=C6
Isomeric SMILES FC1=CC=C(CC2=NNC(=O)C3=C2C=CC=C3)C=C1C(=O)N4CCC5=NC(OCCCN6CCCCC6)=NC=C5C4
InChI InChI=1S/C31H33FN6O3/c32-26-10-9-21(18-28-23-7-2-3-8-24(23)29(39)36-35-28)17-25(26)30(40)38-15-11-27-22(20-38)19-33-31(34-27)41-16-6-14-37-12-4-1-5-13-37/h2-3,7-10,17,19H,1,4-6,11-16,18,20H2,(H,36,39)
InChI Key FGGDDPHGBCQQLG-UHFFFAOYSA-N
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
poly(ADP-ribose) polymerase 1 Hs Inhibitor Inhibition - - - 1
[1]