Poly(ADP-ribose) polymerases (PARPs) are a relatively large family of enzymes that catalyse the transfer of ADP-ribose units from NAD+ to acceptor proteins. They are involved in key cellular functions including DNA repair, telomere integrity, gene expression, cell division, cell survival and cell death. UPF 1069 is a specific PARP2 inhibitor with IC50 of 0.3 M, which is about 27 times more selective than PARP1. 10 µM UPF-1069 was able to reduce PARP activity by 80% in PARP-1-deficient fibroblasts, but only slightly inhibited the enzymic activity in wild-type fibroblasts. The effect of UPF-1069 on organotypic hippocampal slices exposed to 20 min OGD (oxygen-glucose deprivation) was tested at concentrations (0.1–1 µM) selectively acting on PARP-2. It significantly enhanced CA1 hippocampal damage. UPF-1069 displayed a significant neuroprotective activity both at a concentration (1 µM) selectively acting on PARP-2 and at a concentration (10 µM) that inhibits both PARP-1 and PARP-2 activities[2].
UPF 1069 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PARP2 FL
1000 nM
Evaluation of UPF 1069 inhibition on PARP2 FL, IC50 of 1000 nM
J Med Chem. 2017 Feb 23;60(4):1262-1271.
PARP1 FL
145 nM
Evaluation of UPF 1069 inhibition on PARP1 FL, IC50 of 145 nM
J Med Chem. 2017 Feb 23;60(4):1262-1271.
PARP3 FL
1300 nM
Evaluation of UPF 1069 inhibition on PARP3 FL, IC50 of 1300 nM
J Med Chem. 2017 Feb 23;60(4):1262-1271.
PARP14 ART
5700 nM
Evaluation of UPF 1069 inhibition on PARP14 ART, IC50 of 5700 nM
J Med Chem. 2017 Feb 23;60(4):1262-1271.
PARP10 FL
7100 nM
Evaluation of UPF 1069 inhibition on PARP10 FL, IC50 of 7100 nM
J Med Chem. 2017 Feb 23;60(4):1262-1271.
Human Dermal Fibroblasts (HDFs)
10 mM
2 h
To verify the repair effect of low-dose ALA-PDT on photoaged HDFs by inhibiting the BER signaling pathway. The results showed that UPF1069 significantly increased the proportion of SA-β-gal-positive cells, increased the proportion of G2/M phase cells, and increased the expression of aging-related proteins P16, P21, P53, while decreasing the expression of the BER pathway key protein MUTYH.
J Cell Mol Med. 2024 Jul;28(14):e18536.
mouse mixed cortical cell cultures
1–10 μM
60 min
UPF-1069 at 1–10 mmol·L⁻¹ significantly reduced post-ischaemic damage in mouse mixed cortical cells exposed to OGD.
Br J Pharmacol. 2009 Jul;157(5):854-62.
rat organotypic hippocampal slices
0.01–1 μM
20–30 min
UPF-1069 at 0.01–1 mmol·L⁻¹ caused a concentration-dependent exacerbation (up to 155%) of OGD-induced CA1 pyramidal cell death.
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