Adenosine Thiamine Triphosphate (AThTP) Inhibits Poly(ADP-Ribose) Polymerase-1 (PARP-1) Activity

Traditional cancer treatment includes surgery, chemotherapy, radiotherapy and immunotherapy that are clinically beneficial, but are associated with drawbacks such as drug resistance and side effects. In quest for better treatment, many new molecular targets have been introduced in the last few decades. Finding new molecular mechanisms encourages researchers to discover new anticancer agents. Exploring the mechanism of action also facilitates anticipation of potential resistance mechanisms and optimization of rational combination therapies. The write up describes the leading molecular mechanisms for cancer therapy, including mTOR, tyrosine Wee1 kinase (WEE1), Janus kinases, PI3K/mTOR signaling pathway, serine/threonine protein kinase AKT, checkpoint kinase 1 (Chk1), maternal embryonic leucine-zipper kinase (MELK), DNA methyltransferase I (DNMT1), poly (ADP-ribose) polymerase (PARP)-1/-2, sphingosine kinase-2 (SK2), pan-FGFR, inhibitor of apoptosis (IAP), murine double minute 2 (MDM2), Bcl-2 family protein and reactive oxygen species 1 (ROS1). Additionally, the manuscript reviews the anticancer drugs currently under clinical trials.

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Resveratrol inhibits inflammatory signaling implicated in ionizing radiation-induced premature ovarian failure through antagonistic crosstalk between silencing information regulator 1 (SIRT1) and poly(ADP-ribose) polymerase 1 (PARP-1)

Biochemical Pharmacology ◽

10.1016/j.bcp.2016.01.019 ◽

2016 ◽

Vol 103 ◽

pp. 140-150 ◽

Cited By ~ 35

Author(s):

Riham Soliman Said ◽

Ebtehal El-Demerdash ◽

Ahmed Shafik Nada ◽

Mohamed M. Kamal

Keyword(s):

Ionizing Radiation ◽

Premature Ovarian Failure ◽

Ovarian Failure ◽

Inflammatory Signaling ◽

Radiation Induced ◽

Parp 1

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Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes

Cellular and Molecular Life Sciences ◽

10.1007/s00018-009-0105-4 ◽

2009 ◽

Vol 66 (19) ◽

pp. 3219-3234 ◽

Cited By ~ 39

Author(s):

Rosy El Ramy ◽

Najat Magroun ◽

Nadia Messadecq ◽

Laurent R. Gauthier ◽

François D. Boussin ◽

...

Keyword(s):

Genome Integrity ◽

Parp 1

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PARP-1 deregulation in multiple sclerosis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217319894604 ◽

2019 ◽

Vol 5 (4) ◽

pp. 205521731989460 ◽

Cited By ~ 1

Author(s):

Maria Meira ◽

Claudia Sievers ◽

Francine Hoffmann ◽

Heidi Bodmer ◽

Tobias Derfuss ◽

...

Keyword(s):

Multiple Sclerosis ◽

Parp 1

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Discovery of pyrano[2,3-d]pyrimidine-2,4-dione derivatives as novel PARP-1 inhibitors: design, synthesis and antitumor activity

RSC Advances ◽

10.1039/d0ra10321g ◽

2021 ◽

Vol 11 (8) ◽

pp. 4454-4464

Author(s):

Nour E. A. Abd El-sattar ◽

Eman H. K. Badawy ◽

Eman Z. Elrazaz ◽

Nasser S. M. Ismail

Keyword(s):

Cell Death ◽

Dna Repair ◽

Antitumor Activity ◽

Cancer Cell ◽

Cytotoxic Agents ◽

Repair Mechanism ◽

Design Synthesis ◽

Parp 1

PARP-1 are involved in DNA repair damage and so PARP-1 inhibitors have been used as potentiators in combination with DNA damaging cytotoxic agents to compromise the cancer cell DNA repair mechanism, resulting in genomic dysfunction and cell death.

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Pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5-amines as Potential Cytotoxic Agents against Human Neuroblastoma

Pharmaceuticals ◽

10.3390/ph14080750 ◽

2021 ◽

Vol 14 (8) ◽

pp. 750

Author(s):

Zahira Tber ◽

Mohammed Loubidi ◽

Jabrane Jouha ◽

Ismail Hdoufane ◽

Mümin Alper Erdogan ◽

...

Keyword(s):

Cell Line ◽

Drug Exposure ◽

Caspase 3 ◽

Biological Activities ◽

Neuroblastoma Cell ◽

Neuroblastoma Cell Line ◽

Cytotoxic Agents ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Parp 1

We report herein the evaluation of various pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5-amines as potential cytotoxic agents. These molecules were obtained by developing the multicomponent Groebke–Blackburn–Bienaymé reaction to yield various pyrido[2′,1′:2,3]imidazo[4,5-c]quinolines which are isosteres of ellipticine whose biological activities are well established. To evaluate the anticancer potential of these pyrido[2′,1′:2,3]imidazo[4,5-c]isoquinolin-5-amine derivatives in the human neuroblastoma cell line, the cytotoxicity was examined using the WST-1 assay after 72 h drug exposure. A clonogenic assay was used to assess the ability of treated cells to proliferate and form colonies. Protein expressions (Bax, bcl-2, cleaved caspase-3, cleaved PARP-1) were analyzed using Western blotting. The colony number decrease in cells was 50.54%, 37.88% and 27.12% following exposure to compounds 2d, 2g and 4b respectively at 10 μM. We also show that treating the neuroblastoma cell line with these compounds resulted in a significant alteration in caspase-3 and PARP-1 cleavage.

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