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.
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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 |