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PARG clears away the poly(ADP-ribose) chains that PARP enzymes lay down at damaged DNA. Blocking it is meant to deepen the replication stress some cancers already live with, as a partner or alternative to PARP inhibitors; two PARG inhibitors are in trials.
PARG (chromosome 10q11.23) is the enzyme that degrades poly(ADP-ribose) by cutting the bonds between its ribose units; the poly(ADP-ribose) made after DNA damage lasts only briefly because PARG removes it rapidly (UniProt Q86W56). A 2020 review in Genes & Development describes PARG inhibitors as exploiting and exacerbating the replication deficiencies of cancer cells and as possible complements to PARP inhibitors, which act through synthetic lethality with mutations in DNA repair genes (Slade, doi:10.1101/gad.334516.119). In OnCo, DAT-2645 is an oral PARG inhibitor for tumours with BRCA1/2 loss of function or other DNA repair defects, and ETX-19477 an oral PARG inhibitor aimed at replication stress and fork-protection defects.
In plain words · PARG clears away the poly(ADP-ribose) chains that PARP enzymes lay down at damaged DNA. Blocking it is meant to deepen the replication stress some cancers already live with, as a partner or alternative to PARP inhibitors; two PARG inhibitors are in trials.
PARG clears away the poly(ADP-ribose) chains that PARP enzymes lay down at damaged DNA. Blocking it is meant to deepen the replication stress some cancers already live with, as a partner or alternative to PARP inhibitors; two PARG inhibitors are in trials.
Mainly an exo-glycohydrolase that releases ADP-ribose from poly(ADP-ribose) chains; it cannot remove the last ADP-ribose attached to a protein (UniProt Q86W56). It reverses what PARP1 and PARP2 build at DNA lesions.
2 products aim at PARG: small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Mainly an exo-glycohydrolase that releases ADP-ribose from poly(ADP-ribose) chains; it cannot remove the last ADP-ribose attached to a protein (UniProt Q86W56). It reverses what PARP1 and PARP2 build at DNA lesions.
DAT-2645 is an experimental small molecule from Danatlas Pharmaceuticals, in phase 2 trials for solid tumours with BRCA1/2 or DNA damage repair defects and BRCA-mutated or HRD-positive ovarian cancer.
ETX-19477 is an experimental small molecule from 858 Therapeutics, in phase 1 trials for advanced solid tumours, BRCA-mutated platinum-resistant ovarian cancer and BRCA-mutated HR-positive, HER2-negative unresectable or metastatic breast cancer.
Query for this target: (TITLE:"PARG" OR ABSTRACT:"PARG" OR TITLE:"poly ADP-ribose glycohydrolase" OR ABSTRACT:"poly ADP-ribose glycohydrolase") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PARG, not a curated reading list.
Shares PARP and the tag pipeline-gap-target.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares DAT-2645, Metastatic cancer (cancer that has spread).
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