Results 141 to 150 of about 5,113 (169)

2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE DERIVATIVES AS INHIBITORS OF PARG

2016
The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R1a, R1b, R1c, R1d, R1e, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions ...
Mcgonagle, Alison, Jordan,, Allan, Waszkowycz,, Bohdan, Hutton,, Colin, Waddell,, Ian, Hitchin, James, Smith, Kate, Hamilton, Niall   +7 more
openaire   +1 more source

Abstract NT-117: INHIBITION OF PARG, SENSITIZES OVARIAN CANCER CELLS TO PARP INHIBITORS AND DNA DAMAGING AGENTS

Clinical Cancer Research, 2019
Abstract BACKGROUND: Poly(ADP-ribose) glycohydrolase (PARG) is responsible poly(ADP-ribose) (PAR) catabolism, which is synthesized by poly(ADP-ribose) polymerases (PARPs) at the site of DNA single-strand breaks (SSB). Faulty PAR formation or disintegration inhibits SSB repair.
Emad Matanes, Tahira Baloch, David Octeau, Roy Kessous, Liron Kogan, Ido Laskov, Walter Gotlieb, Amber Yasmeen   +7 more
openaire   +1 more source

Abstract C39: First-in-class inhibitors of the putatively undruggable DNA repair target Poly(ADP-ribose) glycohydrolase (PARG)

Molecular Cancer Therapeutics, 2015
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 (PARPs). PARG depletion, using RNAi, results in several effects such as PAR chain persistence, progression of single- to double ...
Bohdan Waszkowycz, Dominic James, Ben Acton, Emma Fairweather, Sam Fritzl, Niall Hamilton, Nicola Hamilton, Sarah Holt, James Hitchen, Colin Hutton, Stuart Jones, Allan Jordan, Alison McGonagle, Daniel Mould, Helen Small, Kate Smith, Alexandra Stowell, Ian D. Waddell, Donald Ogilvie   +18 more
openaire   +1 more source

Abstract CT288: First-in-human study of oral PARG inhibitor SYN608 in advanced solid tumors

Cancer Research
Abstract Background: SYN608 is a novel, selective, orally bioavailable poly(ADP-ribose) glycohydrolase (PARG) inhibitor. PARG plays a critical role in the DNA damage response by reversing protein PARylation and maintaining dynamic balance with PARP activity.
Jin Li, Xiaohua Wu, Qi Dang, Ke Wang, Zhengbo Song, Jun Zhou, Yujia Zhang, Jian Zhang, Jiajia Li, Weina Shen, Shengjie Yang, Hongli Li, Lu Sun, Liyan Zhou, Jianan Jin, Duo Wu, Yue Xie, Xuzhen Tang, Chao Kan, Song Shi, Hu He, Song Liu, Xiaochun Yu   +22 more
openaire   +1 more source

Abstract 7148: Small molecule inhibitor of FEN1 nuclease utilizing a novel metal-binding pharmacophore synergizes with inhibitors of USP1, PARP, PARG and ATR

Cancer Research
Abstract Flap endonuclease 1 (FEN1) is a structure-specific metallonuclease that cleaves 5’ DNA flaps during replication and repair. FEN1 is an attractive target for development of anticancer therapeutics because it is overexpressed in many tumor types and has a large number of synthetic lethality partners including genes in Homologous ...
Jason Munguia, Sanjay Agarwalla, Elaine Guo, Dave Martin, Junhua Fan, Dave Lonergan, David Puerta, Zachary Zimmerman, Konstantin Taganov   +8 more
openaire   +1 more source

“PARG Inhibitors’ Success: A Long Way to Go!”

Current Enzyme Inhibition, 2015
Anuradha Pandey, Pooja Makhija, Prakash G.Chandak, Anil Bhanudas Gaikwad   +3 more
openaire   +1 more source

Pharmacological characterisation of novel, cell active, inhibitors of Poly(ADP-ribose glycohydrolase (PARG)

2014
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 persistence, progression of
Waddell, Ian, James, Dominic, Jordan, Allan, Hamilton, Nicola, McGonagle, Alison, Smith, Kate, Stowell, Alexandra, Waszkowycz, Bohdan, Ogilvie, Donald   +8 more
openaire   +1 more source

Abstract 3909: PARG inhibitor sensitivity is correlated with accumulation of single strand DNA gaps in preclinical models of ovarian cancer

Cancer Research
Abstract Poly (ADP-ribose) glycohydrolase (PARG) is a dePARylating enzyme which promotes DNA repair in conjunction with PARP1 by removal of poly (ADP-ribose) (PAR). Loss or inhibition of PARG results in replication stress and sensitizes cancer cells to DNA damaging agents, suggesting it is a potential therapeutic target for cancer ...
Ramya Ravindranathan, Ozge Somuncu, Yuqing Jiao, Alexandre André B A da Costa, Benjamin P Lamarre, David B Martignetti, Gabriella A Zambrano, Sirisha Mukkavalli, Joyce Liu, Bose Kochupurakkal, Jean-Bernard Lazaro, Kalindi Parmar, Geoffrey I Shapiro, Alan D. D'Andrea   +13 more
openaire   +1 more source

Inhibition of PARG sensitizes ovarian cancer cells to PARP inhibitors and DNA damaging agents

Gynecologic Oncology, 2020
E. Matanes, L. Kogan, V. López-Ozuna, C. Mitric, O. Raban, N. Eisenberg, T. Baloch, S. Salvador, S. Lau, W.H. Gotlieb, A. Yasmeen   +10 more
openaire   +1 more source

Abstract 4263: QX-001352 is a novel and specific inhibitor of PARG with potentially BIC in vitro and in vivo anti-tumor efficacy

Cancer Research
Abstract When DNA is damaged one of the critical steps is the addition of Poly-ADP-ribose (PAR) chains to target proteins. Poly ADP-ribose polymerase 1 (PARP1) is an enzyme that adds PAR chains to target DNA repair proteins including itself.
Dafydd Thomas, Xianhai Huang, Vijay Reddy, Wayne Tang   +3 more
openaire   +1 more source