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别名:
1-[（1,3-二甲基-1H-吡唑-5-基）甲基] -1,2,3,4-四氢-N-（1-甲基环丙基）-3-[（2-甲基-5-噻唑基]甲基] -2,4-二氧代-6-喹唑啉磺酰胺
经验公式（希尔记法）:
C23H26N6O4S2
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生化/生理作用
PDD00017273 是聚（ADP-核糖）糖水解酶（PARG）的高效和选择性抑制剂，可抑制 ADP-核糖聚合物的 O-糖苷键的水解。 经证明 PARG 参与单链 DNA 断裂的修复。 PDD00017273 对 PARG 具有选择性，EC50 = 26 nM，相较而言，对 PARP1 和 ARH3 的值为 30 μM
PDD00017273 本质上是细胞可透过性的。它用于特异性杀死某些同源重组（HR）蛋白（例如乳腺癌基因 1/2（BRCA1/2））中有缺陷的细胞。
WGK
WGK 3
闪点(°F)
Not applicable
闪点(°C)
Not applicable
Radiosensitization with an inhibitor of poly (ADP-ribose) glycohydrolase: A comparison with the PARP1/2/3 inhibitor olaparib.
Gravells P, et al.
DNA Repair, 61, 25-36 (2018)
Polly Gravells et al.
DNA repair, 61, 25-36 (2017-11-28)
Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins. Inhibitors of PARPs have become an exciting and real prospect for monotherapy and as sensitizers to ionising radiation (IR). The
Dominic I James et al.
ACS chemical biology, 11(11), 3179-3190 (2016-10-01)
The enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the repair of DNA single strand breaks (SSBs). However, a detailed understanding of its mechanism of action has been hampered by a lack of credible, cell-active chemical probes. Herein, we
Tanay Thakar et al.
Nature communications, 11(1), 2147-2147 (2020-05-03)
Upon genotoxic stress, PCNA ubiquitination allows for replication of damaged DNA by recruiting lesion-bypass DNA polymerases. However, PCNA is also ubiquitinated during normal S-phase progression. By employing 293T and RPE1 cells deficient in PCNA ubiquitination, generated through CRISPR/Cas9 gene editing
Evgeniia Prokhorova et al.
Molecular cell, 81(12), 2640-2655 (2021-05-22)
ARH3/ADPRHL2 and PARG are the primary enzymes reversing ADP-ribosylation in vertebrates, yet their functions in vivo remain unclear. ARH3 is the only hydrolase able to remove serine-linked mono(ADP-ribose) (MAR) but is much less efficient than PARG against poly(ADP-ribose) (PAR) chains in vitro.
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