Table 1 Parameters of the DDR model calibrated for preclinical studies 1–4 in HBCx-9.
Parameter | Value for HBCx-9 in studies 1–4 | Description | |||
|---|---|---|---|---|---|
1 | 2 | 3 | 4 | ||
\({t}_{{doub}}\) | 27 | 31 | 34 | 33 | Cell doubling time (h) |
\({r}_{{ssb}}\) | 0.0005 | Rate of endogenous generation of SSB damage (DAU/h) | |||
\({{def}}_{1}\) | 0 | 0 | 0 | 0 | Repair deficiency for pathway 1 (SSB, PARP-mediated) |
\({{def}}_{3}\) | 0 | 0 | 0 | 0 | Repair deficiency for pathway 3 (DSB, PARP-mediated) |
\({{def}}_{2}\) | 0 | 0 | 0 | 0 | Repair deficiency for pathway 2 (SSB, ATR-mediated) |
\({{def}}_{4}\) | 20% | 20% | 10% | 30% | Repair deficiency for pathway 4 (DSB, ATR/HR-mediated) |
Parameter | Value for gartisertib | Description | |||
\({i}_{{a\_ssb}}\) | 7 | Unit ATRi inhibitory effect on pathway 2 (/(mg/L)/h) | |||
\({i}_{{a\_dsb}}\) | \({i}_{{a\_ssb}}/2\) | Unit ATRi inhibitory effect on pathway 4 (/(mg/L)/h) | |||
\({o}_{a}\) | 20 | Unit ATRi checkpoint override effect (/DAU/h2/(mg/L)) | |||
\({{cl}}_{a}\) | 0.15 | Rate of clearance of ATRi effects (/h) | |||
Parameter | Value for rucaparib | Value for talazoparib | Description | ||
\({i}_{{p\_ssb}}\) | 5 | 100 | Unit PARPi inhibitory effect on pathway 1 (/(mg/L)/h) | ||
\({i}_{{p\_dsb}}\) | \({i}_{{p\_ssb}}\) | \({i}_{{p\_ssb}}\) | Unit PARPi inhibitory effect on pathway 3 (/(mg/L)/h) | ||
\({i}_{{p\_fork}}\) | 0.5 | 170 | Unit PARPi inhibitory effect on replication fork damage (/(mg/L)/h) | ||
\({{cl}}_{p}\) | 0.15 | 0.15 | Rate of clearance of PARPi SSB/DSB repair inhibition effect (/h) | ||
\({{cl}}_{{p\_fork}}\) | 0.45 | 0.45 | Rate of clearance of PARPi replication fork damage repair inhibition effect (/h) | ||
