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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