Last update 01 Nov 2024

PARP1 x DNA

Last update 01 Nov 2024

Basic Info

Related Targets

PARP1DNA

Drugs associated with PARP1 x DNA

Temozolomide/Senaparib

Target

DNA x PARP1

Mechanism

DNA inhibitors [+2]

Active Org.

IMPACT Therapeutics, Inc.

Originator Org.

IMPACT Therapeutics, Inc.

Active Indication

Small Cell Lung Cancer

Inactive Indication-

Drug Highest PhasePhase 1/2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PARP1 x DNA

100 Translational Medicine associated with PARP1 x DNA

0 Patents (Medical) associated with PARP1 x DNA

Literatures (Medical) associated with PARP1 x DNA

01 Dec 2024·Biophysical Chemistry

Characterization of PARP1 binding to c-KIT1 G-quadruplex DNA: Insights into domain-specific interactions

Article

Author: Rajakumara, Eerappa ; Deeksha, Waghela ; Singh, Dagur Hanuman ; Hanuman Singh, Dagur

Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme involved in catalyzing Poly-(ADP-ribosyl)ation. PARP1 binds to different forms of DNA and DNA breaks and thus plays important roles in several cellular processes, including DNA damage repair, cell cycle regulation, chromatin remodeling, and maintaining genomic stability. In this study, we conducted biochemical and biophysical characterization of PARP1 binding to G-quadruplex DNA (G4-DNA). Our investigation identified ZnF1, ZnF3, and WGR as the critical domains to mediate PARP1 binding to G4-c-KIT1. Also, our results show that these domains together show cooperativity for G4-c-KIT1 recognition. Further, we establish that the presence of an oxidized (5-carboxylcytosine) base in the loop region of G4-c-KIT1 (G4-5caC-cKIT1) does not affect its recognition by PARP1. Both G4-c-KIT1 and G4-5caC-cKIT1 are potent stimulators of PARP1's catalytic activity. Our study advances the understanding of PARP1's versatile DNA binding capabilities for G4-c-KIT1 DNA irrespective of the oxidation/ modification in the DNA base. These insights into PARP1's domain-specific contributions to G4-c-KIT1 DNA recognition and catalysis expand our knowledge of its multifaceted roles in DNA repair and genome maintenance.

23 Dec 2021·Journal of Medicinal ChemistryQ1 · MEDICINE

Design and Synthesis of Indenoisoquinolines Targeting Topoisomerase I and Other Biological Macromolecules for Cancer Chemotherapy

Q1 · MEDICINE

Review

Author: Cushman, Mark

The discovery that certain indenoisoquinolines inhibit the religation reaction of DNA in the topoisomerase I-DNA-indenoisoquinoline ternary complex led to a structure-based drug design research program which resulted in three representatives that entered Phase I clinical trials in cancer patients at the National Cancer Institute. This has stimulated a great deal of interest in the design and execution of new synthetic pathways for indenoisoquinoline production. More recently, modulation of the substitution pattern and chemical nature of substituents on the indenoisoquinoline scaffold has resulted in a widening scope of additional biological targets, including RXR, PARP-1, MYC promoter G-quadruplex, topoisomerase II, estrogen receptor, VEGFR-2, HIF-1α, and tyrosyl DNA phosphodiesterases 1 and 2. Furthermore, convincing evidence has been advanced supporting the potential use of indenoisoquinolines for the treatment of diseases other than cancer. The rapidly expanding indenoisoquinoline knowledge base has provided a firm foundation for further advancements in indenoisoquinoline chemistry, pharmacology, and therapeutics.

01 Sep 2019·DNA RepairQ3 · MEDICINE

XRCC1 protein; Form and function

Q3 · MEDICINE

Review

Author: Caldecott, Keith W

The human gene that encodes XRCC1 was cloned nearly thirty years ago but experimental analysis of this fascinating protein is still unveiling new insights into the DNA damage response. XRCC1 is a molecular scaffold protein that interacts with multiple enzymatic components of DNA single-strand break repair (SSBR) including DNA kinase, DNA phosphatase, DNA polymerase, DNA deadenylase, and DNA ligase activities that collectively are capable of accelerating the repair of a broad range of DNA single-strand breaks (SSBs). Arguably the most exciting aspect of XRCC1 function that has emerged in the last few years is its intimate relationship with PARP1 activity and critical role in preventing hereditary neurodegenerative disease. Here, I provide an update on our current understanding of XRCC1, and on the impact of hereditary mutations in this protein and its protein partners on human disease.

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