VE-821 at 1 µM reduced pancreatic cancer cell clonogenic survival after irradiation under normoxia and 0.5% O2. The effect depended on scheduling: in PSN-1 cells, addition 24 h after irradiation retained radiosensitization, whereas addition at 48 h lost it. These are cell-culture findings. [1]
In MCF10A breast epithelial cells, VE821 pretreatment reduced the hydroxyurea-induced APOBEC3 deamination response measured in cell lysates. This finding supports a role for ATR signaling in that stress response; it does not establish direct APOBEC inhibition or prevention of tumor mutations. [2]
Suppression of damage-induced Chk1 phosphorylation
Cell-based study · PSN-1 and MiaPaCa-2 pancreatic cancer cells [1]
VE-821 reduced induced Chk1 Ser345 phosphorylation in cells exposed to gemcitabine, radiation or both. Total Chk1 and β-actin were shown as controls. This is a cellular signaling result, not a purified-enzyme potency measurement.
Literature-Reported Treatment Conditions
- Treatment concentration
- 1 µM VE-821; gemcitabine 100 nM; radiation 6 Gy
- Exposure duration
- Drugs added 1 h before irradiation and retained; lysates at 2 h after irradiation.
- Method
- Western blot of phosphorylated and total Chk1 with β-actin control.
- Vehicle
- DMSO stock; final vehicle percentage not specified in read methods.
- Co-treatment
- Gemcitabine, radiation, or both, compared with matched conditions without VE-821.
- Reported limits
- Exact replicate count for panel A is not separately specified; no fitted IC50 is reported for this experiment.
Methods and source locations
Compound reported in the paper: VE-821
Evidence concerns the paper’s named VE-821 material and experimental model; it does not validate the current Adooq lot or establish human efficacy.
Figure 1A and caption; Results, first paragraph; Methods, Drugs/cell lines and Western blot
Damage-induced Chk1 Ser345 phosphorylation: Western blot, with total Chk1 and β-actin shown. — Figure 1A and caption; Results, first paragraph; Methods, Drugs/cell lines and Western blot
Clonogenic radiosensitization under normoxia and hypoxia
Cell-based study · MiaPaCa-2, PSN-1, PANC-1 and primary PancM pancreatic cancer cells under normoxia; MiaPaCa-2, PSN-1 and PancM under 0.5% O2 [1]
VE-821 lowered clonogenic survival after irradiation under both oxygen conditions. Hypoxic cultures remained more radioresistant than oxic cultures. Scheduling in PSN-1 mattered: addition 24 h after radiation retained radiosensitization, whereas addition at 48 h lost it.
Literature-Reported Treatment Conditions
- Treatment concentration
- 1 µM VE-821; radiation dose series shown at 0, 2, 4 and 6 Gy
- Exposure duration
- Standard schedule: added 1 h before irradiation, removed 72 h after irradiation; colonies assessed after 10–21 days. Hypoxia acclimatization 6 h before drug addition, returning to normoxia 1 h after irradiation (Figure 2 diagram).
- Method
- Clonogenic assay with matched vehicle and unirradiated controls; Figure 1C survival fractions account for relevant plating efficiencies.
- Vehicle
- DMSO-treated controls; final percentage not specified.
- Co-treatment
- Ionizing radiation; no gemcitabine in these selected comparisons.
- Reported limits
- Absolute surviving fractions and unirradiated plating efficiencies are not transcribed from curves; SI Figure S1B was not retrieved. Figure 2 caption timing is best read with its explicit -7 h to +1 h diagram.
Methods and source locations
Compound reported in the paper: VE-821
Evidence concerns the paper’s named VE-821 material and experimental model; it does not validate the current Adooq lot or establish human efficacy.
Figures 1C–D and 2A–B with captions; Results, radiosensitization and hypoxia; Methods, Clonogenic assay
Colony-forming survival after radiation: Clonogenic survival; no numerical effect size inferred from plotted curves. — Figure 1D; Figure 2A–B and captions
PSN-1 clonogenic radiosensitization at 4 Gy: Matched scheduling comparison; relevant unirradiated plating efficiency accounted for in reported surviving fraction. — Figure 1C and associated Results paragraph
ATR-pathway inhibition reduces a stress-induced cellular deamination response
Cell-based study · Non-tumorigenic MCF10A breast epithelial cells [2]
VE821 reduced the hydroxyurea-induced APOBEC3 cytidine-deamination response. ATM inhibition showed a smaller reduction in the same comparison. This cell-lysate readout does not demonstrate direct inhibition of an APOBEC enzyme or reduced mutation accumulation in tumors.
Literature-Reported Treatment Conditions
- Treatment concentration
- VE821 1 µM; hydroxyurea 2 mM; comparator KU55933 10 µM
- Exposure duration
- ATM or ATR inhibitor pretreatment for 24 h, followed by hydroxyurea for a further 48 h before lysis.
- Method
- Gel-based cytidine-deamination assay on protein-normalized cell lysates.
- Vehicle
- Panel-specific vehicle composition not specified in the read main text.
- Co-treatment
- Hydroxyurea; untreated, inhibitor-only and hydroxyurea-only conditions shown in Figure 5a.
- Reported limits
- No panel-specific replicate number, quantitative effect size or error estimate supplied in the read Figure 5a caption. Supplementary cytotoxicity/cell-cycle and siRNA panels were not acquired and are not used to claim absence of confounding.
Methods and source locations
Compound reported in the paper: VE-821
Evidence concerns the paper’s named VE-821 material and experimental model; it does not validate the current Adooq lot or establish human efficacy.
Figure 5a and caption; Results Sec8; Methods Sec13, Sec14 and Sec17
Hydroxyurea-induced APOBEC3 cytidine-deamination activity in MCF10A lysates: Qualitative gel-based deamination readout, with untreated and inhibitor-only controls. — Figure 5a and caption; Results Sec8; Methods Sec13, Sec14 and Sec17
