Results 131 to 140 of about 5,113 (169)

Design and synthesis of phenolic hydrazide hydrazones as potent poly(ADP-ribose) glycohydrolase (PARG) inhibitors

Bioorganic & Medicinal Chemistry Letters, 2014
Poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) are enzymes responsible for catalyzing the formation and degradation of poly(ADP-ribose) (PAR) polymers, respectively. Activation of PARP has been shown to be involved in cell death induced by genotoxic stimuli.
Rafiqul, Islam, Fumiaki, Koizumi, Yasuo, Kodera, Kengo, Inoue, Tadashi, Okawara, Mitsuko, Masutani   +5 more
openaire   +2 more sources

Abstract 6184: Pre-clinical study of SYX3759, a novel PARG inhibitor for the treatment of homologous recombination deficient malignancies

Cancer Research, 2023
Abstract Although PARP inhibitors (PARPi) are very successful on the treatment of BRCA-mutant cancer, the tumor spectrum targeted by PARPi is quite narrow. Interestingly, Poly(ADP-ribose) Glycohydrolase (aka PARG), the major dePARylation enzyme, has emerged as a promising therapeutic target for cancer treatment. Here, we have developed a
Xuzhen Tang, Yaqi Cui, Lanqiao Zhang, Huihui Jin, Zeqiong Xu, Hu He, Chongxun Ge, Song Liu, Xiaochun Yu, Song Shi   +9 more
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Abstract 245: Expanding the therapeutic window of PARP inhibitors by co-administering PARG inhibitors.

Cancer Research
Abstract Background: Homologous recombination (HR) deficiency sensitizes tumors to PARP inhibitors (PARPi), which are standard-of-care for HR-deficient cancers. Despite their efficacy, clinical use of PARPi is limited by on-target toxicity, particularly anemia, leading to dose reductions and ...
Giacomo G. Rossetti, Michalis Petropoulos, Theodoros Rampias, Thanos D. Halazonetis   +3 more
openaire   +1 more source

Abstract 3714: Optimisation of quinazolinedione sulphonamides as novel inhibitors of poly(ADP Ribose) glycohydrolase (PARG)

Cancer Research, 2016
Abstract The macrodomain protein poly(ADP ribose) glycohydrolase (PARG) has been shown to be a critical component in the repair of single stand DNA breaks and counteracts the function of the ARTD family of poly(ADP ribose) polymerases, commonly known as the PARPs.
Kate Smith, Ben Acton, Dominic James, Cliff Jones, Stuart Jones, Allan Jordan, Nicola Hamilton, Alison McGonagle, Daniel Mould, Helen Small, Alex Stowell, Julie Tucker, Ian Waddell, Bohdan Waszkowycz, Donald Ogilvie   +14 more
openaire   +1 more source

Abstract 2667: PARG inhibition augments CHK1 inhibitor-induced replication stress and synergistically kills ovarian cancer cells

Cancer Research, 2023
Abstract Ovarian cancer (OC) is one of the leading causes of cancer-related deaths in women in the United States. PARP inhibitors showed promising clinical responses; however, most of the patients eventually relapse and succumb to the resistant disease. Currently, it lacks effective therapies to prevent and treat OC, which warrants novel
Ganesh Acharya, Chinnadurai Mani, Mark B. Reedy, Komaraiah Palle   +3 more
openaire   +1 more source

Abstract 2745: Pharmacological characterisation of cell active inhibitors of Poly(ADP-ribose) glycohydrolase (PARG)

Cancer Research, 2014
Abstract Poly(ADP-ribose) glycohydrolase (PARG) is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers, thereby reversing the effects of poly(ADP-ribose) polymerases. Total PARG deficiency leads to cell death whilst PARG depletion, using RNAi, leads to pleiotropic effects such as PAR chain ...
Dominic James, Allan Jordan, Nicola Hamilton, Alison McGonagle, Kate Smith, Alexandra Stowell, Ian Waddell, Bohdan Waszkowycz, Donald Ogilvie   +8 more
openaire   +1 more source

Abstract 7112: Preclinical profile of novel and potent small molecule inhibitors of PARG

Cancer Research
Abstract Poly(ADP-ribose) glycohydrolase (PARG) is primary enzyme involved in the dePARylation process of DNA repair, specifically in the single strand break repair (SSBRs). PARG is a macrodomain protein with exo- and endo-glycohydrolase activity that liberates free ADP-ribose and PAR chains, respectively.
Sukanya Patra, Manoj Pothuganti, Githavani Kummari, Venu Sankeshi, Jyothipriya Kapaka, Navnath Karche, Ramamohan Mekala, Srikant Viswanadha   +7 more
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Abstract 6972: Discovery of XNW29016, a PARG inhibitor for HRD cancer therapy

Cancer Research
Abstract DNA damage repair enzymes are promising targets as genomic instability and DNA repair defects are important characteristics of cancer cells PARylation catalysed by PARP1/2 is a kind of reversible protein modification, which has central functions in maintaining genome stability.
Yonghan Hu, Haiyang Wei, Dawei Wan, Ben Ma, Jiajing Xu, Shihua Wang, Liang Kong, Zhe Zhang, Yuanbao Li, Zhenwei Wu, Yuzhen Hou, Wengui Wang, Xiaojun Liu, Meijie Le, Jing Qiang   +14 more
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Abstract 3715: Benzimidazolone sulphonamides - potent, selective and drug-like inhibitors of poly(ADP Ribose) Glycohydrolase (PARG)

Cancer Research, 2016
Abstract In recent years, many proteins involved in DNA repair, such as ATR, ATM and PARP, have received considerable attention as potential points of therapeutic intervention in cancer. Indeed, these efforts have recently delivered several agents into clinical evaluation or FDA regulatory approval.
Allan Jordan, Ben Acton, Nicola Hamilton, James Hitchin, Colin Hutton, Dominic James, Cliff Jones, Stuart Jones, Alison McGonagle, Helen Small, Kate Smith, Alex Stowell, Julie Tucker, Ian Waddell, Bohdan Waszkowycz, Donald Ogilvie   +15 more
openaire   +1 more source

Abstract 5515: In vivo efficacy of the PARG inhibitor Gallotannin against triple negative breast cancer.

Cancer Research, 2013
Abstract Breast cancer patients whose tumors fall into the triple negative category have the poorest clinical outcomes. These patients are at high risk for metastatic recurrence and have poor overall survival. Clearly, new therapeutic strategies are needed to combat triple negative tumors both at the time of onset and if necessary, at ...
Tiejun Zhao, Qiang Sun, Amanda Lovato, Sonia del Rincon, Michael Witcher   +4 more
openaire   +1 more source