Abstract
Poly (ADP-ribose) polymerase-1 (PARP1) is a major member of the PARP superfamily that is involved in DNA damage signalling and other important cellular processes. Here we report the development of a small molecule targeting PARP1 based on the PROTAC strategy. In the MDA-MB-231 cell line, the representative compound 3 can induce significant PARP1 cleavage and programmed cell death.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Line, Tumor
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DNA Damage
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Female
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Humans
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Molecular Structure
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Piperidines / chemical synthesis
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Piperidines / chemistry
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Piperidines / pharmacology*
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Poly (ADP-Ribose) Polymerase-1 / antagonists & inhibitors*
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Poly (ADP-Ribose) Polymerase-1 / metabolism
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Poly(ADP-ribose) Polymerase Inhibitors / chemical synthesis
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Poly(ADP-ribose) Polymerase Inhibitors / chemistry
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Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
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Proteolysis
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Piperidines
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Poly(ADP-ribose) Polymerase Inhibitors
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Small Molecule Libraries
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piperidine
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PARP1 protein, human
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Poly (ADP-Ribose) Polymerase-1