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
References
1. Lin S, Jiang Q, Huang X, Xu J, Wu L, Liu Y. (2023)
Synthesis of Novel Dual Target Inhibitors of CDK12 and PARP1 and Their Antitumor Activities in HER2-Positive Breast Cancers.
ACS Omega,. DOI: 10.1021/acsomega.3c02912