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Table 1 Estimated parameters for the protein-based cell cycle and apoptosis model

From: Pharmacodynamic modeling of synergistic birinapant/paclitaxel interactions in pancreatic cancer cells

  Parameter Unit Estimate (CV%) Comment Drug-specific?
Protein interactions model \( {\mathrm{k}}_{\deg_{\mathrm{i}}} \) Synthesis- or degradation rate constant for the turnover of protein i. (protein-specific parameters) h−1 0.649 (16.8) Bcl2, cIAP1 and pNF-κB (pp65) N
0.127 (6.94) IRAK4 N
8.26 × 10− 3 (38.9) pJNK N
3.16 × 10−2 (46.7) pSTAT3 N
0.696 (165) VDAC1 N
2.80 × 10−2 (9.39) ELYS N
0.861 (39.3) ASPP2 N
2.91 × 10−2 (7.41) BAX N
γi-j Power coefficient for an interaction when the synthesis rate of protein i is modified by protein j. (protein-specific parameters) −0.298 (9.31) pNF-κB |- cIAP1 N
1.85 (11.0) BAX < - pNF-κB N
0.768 (8.36) BCL2 < - pNF-κB N
1.0 (−a) pSTAT3 < − IRAK4
VDAC1 < - pJNK
ASPP2 < - ELYS
N
1.33 (20.9) BCL2 < - pSTAT3 N
−4.16 (8.38) BCL2 |- VDAC1 N
−2.30 (30.3) pSTAT3 |- pJNK N
−9.55 (16.2) BAX |- BAX N
−6.10 (12.6) ELYS |- ELYS N
Ei_x Effect of treatment x on the synthesis rate of protein i (drug-specific parameters) 0.960 (1.76) IRAK4 < - B/P/B + P (StiX) Y
−0.967 (0.503) cIAP1 |- B (InhB) Y
2.22 (12.2) ELYS <- P (StiP) Y
1.0b (−a) pJNK <− B + P (InhB + P) Y
Cell cycle and apoptosis kxx The 1st-order transition rate constant between cell cycle phases or apoptosis stages (cell-specific) h−1 4.48 × 10−2 (8.60) G0/G1 to S (k12) N
0.129 (7.25) S to G2/M (k23) N
8.07 × 10−2 (5.78) G2/M to G0/G1 (k31) N
2.18 × 10−3 (15.6) Live to apoptotic (kap) in the absence of treatment N
1.97 × 10−2 (0.938) Mitosis-arrested to polyploid (kpl) N
Nmax The capacity of cell density 7.43 (14.6) Fold increase compared to seeding density in 6-well plates N
live0 The cell number at the beginning of the study   2.0 × 105
(fixed)
Seeding density in 6-well plates N
Integrated protein-based cell cycle and apoptosis kxx The transition rate constant between cell cycle phases or apoptosis stages (cell-specific) h−1 2.39 × 10−2 (2.01) Normal G2/M to mitotic arrested (kma0) N
0.111 (8.22) Mitotic arrested to apoptosis (kapm0) N
γi Power coefficient for protein i to modify a transition rate constant (protein-specific) −0.532 (0.81) cIAP1 inhibits kap N
−7.72 × 10−2 (13.7) cIAP1 inhibits kapm0 N
0.208 (45.8) BAX stimulates kapm0 N
3 (−a) ELYS stimulates kar N
  1. aValue was fixed
  2. bThe combination (B + P) inhibits the degradation of pJNK completely