Abstract：
:Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a promising class of targeted cancer drugs, but their individual target profiles beyond the PARP family, which could result in differential clinical use or toxicity, are unknown. Using an unbiased, mass spectrometry-based chemical proteomics approach, we generated a comparative proteome-wide target map of the four clinical PARPi, olaparib, veliparib, niraparib, and rucaparib. PARPi as a class displayed high target selectivity. However, in addition to the canonical targets PARP1, PARP2, and several of their binding partners, we also identified hexose-6-phosphate dehydrogenase (H6PD) and deoxycytidine kinase (DCK) as previously unrecognized targets of rucaparib and niraparib, respectively. Subsequent functional validation suggested that inhibition of DCK by niraparib could have detrimental effects when combined with nucleoside analog pro-drugs. H6PD silencing can cause apoptosis and further sensitize cells to PARPi, suggesting that H6PD may be, in addition to its established role in metabolic disorders, a new anticancer target.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Knezevic CE,Wright G,Rix LLR,Kim W,Kuenzi BM,Luo Y,Watters JM,Koomen JM,Haura EB,Monteiro AN,Radu C,Lawrence HR,Rix Udoi
10.1016/j.chembiol.2016.10.011subject
Has Abstractpub_date
2016-12-22 00:00:00pages
1490-1503issue
12eissn
2451-9456issn
2451-9448pii
S2451-9456(16)30389-0journal_volume
23pub_type
杂志文章abstract：:In this issue of Cell Chemical Biology, Harvey et al. (2020) identify 4E14, a sulfhydryl-containing N-acetyltryptophan analog that selectively disrupts binding to the previously undruggable anti-apoptotic BCL2 paralog BFL1, and elucidate a BFL1 conformational change that facilitates 4E14 interaction. These results pro...
journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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pub_type： 评论,杂志文章
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
pub_type： 评论,杂志文章
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
pub_type： 评论,杂志文章
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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doi：10.1016/j.chembiol.2016.02.015
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journal_title：Cell chemical biology
pub_type： 评论,杂志文章
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abstract：:G-quadruplexes are specialized secondary structures in nucleic acids that possess significant conformational polymorphisms. The precise G-quadruplex conformations in vivo and their relevance to biological functions remain controversial and unclear, especially for telomeric G-quadruplexes. Here, we report a novel singl...
journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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journal_title：Cell chemical biology
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abstract：:The glycan ligands recognized by Siglecs, influenza viruses, and galectins, as well as many plant lectins, are not well defined. To explore their binding to asparagine (Asn)-linked N-glycans, we synthesized a library of isomeric multiantennary N-glycans that vary in terminal non-reducing sialic acid, galactose, and N-...
journal_title：Cell chemical biology
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