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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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 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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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 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