Results 11 to 20 of about 6,510 (175)

CHK1 inhibitor induced PARylation by targeting PARG causes excessive replication and metabolic stress and overcomes chemoresistance in ovarian cancer

Cell Death Discovery
Chemoresistance contributes to the majority of deaths in women with ovarian cancer (OC). Altered DNA repair and metabolic signaling is implicated in mediating therapeutic resistance.
Ganesh Acharya, Chinnadurai Mani, Naresh Sah, Karunakar Saamarthy, Robert Young, Mark B. Reedy, Robert W. Sobol, Komaraiah Palle   +7 more
doaj   +4 more sources

PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer. [PDF]

Proc Natl Acad Sci U S A
Poly (ADP-ribose) glycohydrolase (PARG) is a dePARylating enzyme which promotes DNA repair by removal of poly (ADP-ribose) (PAR) from PARylated proteins. Loss or inhibition of PARG results in replication stress and sensitizes cancer cells to DNA-damaging agents.
Ravindranathan R, Somuncu O, da Costa AABA, Mukkavalli S, Lamarre BP, Nguyen H, Grochala C, Jiao Y, Liu J, Kochupurakkal B, Parmar K, Shapiro GI, D'Andrea AD.   +12 more
europepmc   +4 more sources

Prospects for PARG inhibitors in cancer therapy. [PDF]

J Mol Cell Biol
Abstract Poly(ADP-ribose) glycosylhydrolase (PARG) is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose) (PAR), which are primarily found in the nucleus. Along with poly(ADP-ribose) polymerase, PARG regulates the level of PAR in cells, playing a crucial role in DNA maintenance and repair processes ...
Hu Y, Meng Y, Zhuang Z, Li Y, Nan J, Xu N, Ye Z, Jing J.   +7 more
europepmc   +4 more sources

Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality [PDF]

Cancer Cell, 2018
Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have recently entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, drug resistance is a clinical hurdle, and we poorly understand how cancer cells escape the deadly effects of PARPi without restoring the HR pathway.
Ewa Gogola, Wouter W Wiegant, Daniel J Vis   +2 more
exaly   +9 more sources

Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP‐ribose) glycohydrolase inhibitor

FEBS Open Bio
Poly(ADP‐ribose) glycohydrolase (PARG) is a key enzyme involved in poly(ADP‐ribose) (PAR) degradation and is considered a potential anticancer target. We previously investigated resistance mechanisms to the PARG inhibitor PDD00017273 in human colorectal ...
Kaede Tsuda, Yoko Ogino, Akira Sato
doaj   +2 more sources

Radiosensitization with an inhibitor of poly(ADP-ribose) glycohydrolase: A comparison with the PARP1/2/3 inhibitor olaparib [PDF]

DNA Repair, 2018
Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins.
Albert, Ali, Ame, Amit Nathubhai, Audebert, Barkauskaite, Beck, Benhur, Benjamin, Blenn, Boehler, Boulton, Braun, Bridges, Brochu, Bryant, Bryant, Bryant, Calabrese, Chalmers, Chang, Chang, Chang, Chow, Cortes, deMurcia, Ding, Dominic I. James, Donawho, Drean, Dungey, Dungey, Efimova, El-Khamisy, Emma Grant, Erdelyi, Fabbro, Fathers, Feng, Feng, Feng, Fisher, Godon, Gravells, Ha, Helen E. Bryant, Huang, Illuzzi, James, James Neale, Kate M. Smith, Khan, Kim, Le Page, Lee, Lomax, Martin, Medvedeva, Min, Miwa, Morrison, Mueller, Nakadate, Nathubhai, Noel, Okano, Oplustil O'Connor, Ozaki, Polly Gravells, Ray Chaudhuri, Rothkamm, Rulten, Rulten, Saleh-Gohari, Schlicker, Schreiber, Senra, Shall, Shelton, Shirai, Shirai, Slade, Strom, Sugimura, Tripathi, Trucco, Venere, Wang, Wang, Wang, Wieler, Yang, Yeh, Yoshikawa, Zhu   +94 more
core   +4 more sources

Targeting SARS-CoV-2 Nsp3 macrodomain structure with insights from human poly(ADP-ribose) glycohydrolase (PARG) structures with inhibitors [PDF]

Progress in Biophysics and Molecular Biology, 2021
Arrival of the novel SARS-CoV-2 has launched a worldwide effort to identify both pre-approved and novel therapeutics targeting the viral proteome, highlighting the urgent need for efficient drug discovery strategies. Even with effective vaccines, infection is possible, and at-risk populations would benefit from effective drug compounds that reduce the ...
Chris A Brosey, Sarita Namjoshi, Panagiostis Katsonis   +2 more
exaly   +4 more sources

Mono‐galloyl glucose derivatives are potent poly(ADP‐ribose) glycohydrolase (PARG) inhibitors and partially reduce PARP‐1‐dependent cell death [PDF]

British Journal of Pharmacology, 2008
Background and purpose:Maintenance of poly(ADP‐ribose) (PAR) polymers at homoeostatic levels by PAR glycohydrolase (PARG) is central in cell functioning and survival. Yet the pharmacological relevance of PARG inhibitors is still debated. Gallotannin, a complex mixture of hydrolysable tannins from oak gall, inhibits PARG but which of its constituents is
FORMENTINI, LAURA, P. Arapistas, PITTELLI, MARIA, M. Jacomelli, PITOZZI, VANESSA, MENICHETTI, STEFANO, ROMANI, ANNALISA, GIOVANNELLI, LISA, MORONI, FLAVIO, CHIARUGI, ALBERTO   +9 more
exaly   +4 more sources

Intrinsic PARG inhibitor sensitivity is mimicked by TIMELESS haploinsufficiency and rescued by nucleoside supplementation. [PDF]

NAR Cancer
Abstract A subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced by inhibition of TIMELESS, a replisome accelerator.
Coulson-Gilmer C, Littler S, Barnes BM, Brady RM, Anagho HA, Pillay N, Dey M, Macmorland W, Bronder D, Nelson L, Tighe A, Lin WH, Morgan RD, Unwin RD, Nielsen ML, McGrail JC, Taylor SS.   +16 more
europepmc   +6 more sources

PARP and PARG inhibitors in cancer treatment [PDF]

Genes & Development, 2020
Oxidative and replication stress underlie genomic instability of cancer cells. Amplifying genomic instability through radiotherapy and chemotherapy has been a powerful but nonselective means of killing cancer cells. Precision medicine has revolutionized cancer therapy by putting forth the concept of selective targeting of cancer cells. Poly(ADP-ribose)
openaire   +2 more sources