// Created by libAntimony v2.13.0
function STAT3(STAT3tot, pSTAT3, STAT3uStattic)
  STAT3tot - pSTAT3 - STAT3uStattic;
end

STAT3 is "STAT3"

function Function_for_v16(Km16, cMET, kc16, kdeg16, pCbl, rootCompartment)
  (kdeg16 + kc16*pCbl*rootCompartment)*cMET*rootCompartment/(Km16 + cMET*rootCompartment)/rootCompartment;
end

Function_for_v16 is "Function for v16"

function PYK2tot(PYK2, pPYK2)
  PYK2 + pPYK2;
end

PYK2tot is "PYK2tot"

function Stattic(Stattictot, STAT3uStattic)
  Stattictot - STAT3uStattic;
end

Stattic is "Stattic"

function Function_for_v9(EMD, Ki9, Km9, PYK2, kc9a, kc9b, pEGFR, pcMET, rootCompartment)
  (kc9a*pEGFR*rootCompartment + kc9b*pcMET*rootCompartment/(1 + EMD/Ki9))*PYK2*rootCompartment/(Km9 + PYK2*rootCompartment)/rootCompartment;
end

Function_for_v9 is "Function for v9"

function Function_for_v5(Km5, Vmax5, Vs5, pSTAT3, rootCompartment)
  (Vs5 + Vmax5*pSTAT3*rootCompartment/(Km5 + pSTAT3*rootCompartment))/rootCompartment;
end

Function_for_v5 is "Function for v5"

function Function_for_v22(Km22, Vmax22, aPTP, rootCompartment)
  Vmax22*aPTP*rootCompartment/(Km22 + aPTP*rootCompartment)/rootCompartment;
end

Function_for_v22 is "Function for v22"

function Function_for_v7(Km7, PYK2m, Vmax7, rootCompartment)
  Vmax7*PYK2m*rootCompartment/(Km7 + PYK2m*rootCompartment)/rootCompartment;
end

Function_for_v7 is "Function for v7"

function PTP(PTPtot, aPTP)
  PTPtot - aPTP;
end

PTP is "PTP"

function Function_for_v12(Km12, Vmax12, aPTP, kc12, pSTAT3, rootCompartment)
  (Vmax12 + kc12*aPTP*rootCompartment)*pSTAT3*rootCompartment/(Km12 + pSTAT3*rootCompartment)/rootCompartment;
end

Function_for_v12 is "Function for v12"

function Function_for_v10(Km10, Vmax10, aPTP, kc10, pPYK2, rootCompartment)
  (Vmax10 + kc10*aPTP*rootCompartment)*pPYK2*rootCompartment/(Km10 + pPYK2*rootCompartment)/rootCompartment;
end

Function_for_v10 is "Function for v10"

function Function_for_v13(Km13, Vmax13, Vs13, pSTAT3, rootCompartment)
  (Vs13 + Vmax13*pSTAT3*rootCompartment/(Km13 + pSTAT3*rootCompartment))/rootCompartment;
end

Function_for_v13 is "Function for v13"

function Function_for_v21(Km21, PTPtot, aPTP, kc21, pEGFR, rootCompartment)
  kc21*pEGFR*rootCompartment*PTP(PTPtot, aPTP*rootCompartment)/(Km21 + PTP(PTPtot, aPTP*rootCompartment))/rootCompartment;
end

Function_for_v21 is "Function for v21"

function Function_for_v11(Ki3b, Km11, PF396, STAT3tot, STAT3uStattic, kc11, pPYK2, pSTAT3, rootCompartment)
  kc11*(pPYK2*rootCompartment/(1 + PF396/Ki3b))*STAT3(STAT3tot, pSTAT3*rootCompartment, STAT3uStattic*rootCompartment)/(Km11 + STAT3(STAT3tot, pSTAT3*rootCompartment, STAT3uStattic*rootCompartment))/rootCompartment;
end

Function_for_v11 is "Function for v11"

function Function_for_v25(STAT3tot, STAT3uStattic, Stattictot, ka25, kd25, pSTAT3, rootCompartment)
  (ka25*STAT3(STAT3tot, pSTAT3*rootCompartment, STAT3uStattic*rootCompartment)*Stattic(Stattictot, STAT3uStattic*rootCompartment) - kd25*STAT3uStattic*rootCompartment)/rootCompartment;
end

Function_for_v25 is "Function for v25"

function Function_for_v18(Km18, Vmax18, pcMET, rootCompartment)
  Vmax18*pcMET*rootCompartment/(Km18 + pcMET*rootCompartment)/rootCompartment;
end

Function_for_v18 is "Function for v18"

function Function_for_v14(cMETm, kdeg14, rootCompartment)
  kdeg14*cMETm*rootCompartment/rootCompartment;
end

Function_for_v14 is "Function for v14"

function Function_for_v8(PYK2, kdeg8, rootCompartment)
  kdeg8*PYK2*rootCompartment/rootCompartment;
end

Function_for_v8 is "Function for v8"

function Function_for_v20(Km20, Vmax20, aPTP, kc20, pCbl, rootCompartment)
  (Vmax20 + kc20*aPTP*rootCompartment)*pCbl*rootCompartment/(Km20 + pCbl*rootCompartment)/rootCompartment;
end

Function_for_v20 is "Function for v20"

function Function_for_v24(Km24, Vmax24, pERK, rootCompartment)
  Vmax24*pERK*rootCompartment/(Km24 + pERK*rootCompartment)/rootCompartment;
end

Function_for_v24 is "Function for v24"

function Cbl(Cbltot, pCbl)
  Cbltot - pCbl;
end

Cbl is "Cbl"

function Function_for_v17(HGF, Km17, cMET, caHGF, kc17, rootCompartment)
  (kc17*HGF + caHGF)*cMET*rootCompartment/(Km17 + cMET*rootCompartment)/rootCompartment;
end

Function_for_v17 is "Function for v17"

function Function_for_v2(Km2, Vmax2, aPTP, kc2, pEGFR, rootCompartment)
  (Vmax2 + kc2*aPTP*rootCompartment)*pEGFR*rootCompartment/(Km2 + pEGFR*rootCompartment)/rootCompartment;
end

Function_for_v2 is "Function for v2"

function Function_for_v4(EGFRub, Km4, Vmax4, rootCompartment)
  Vmax4*EGFRub*rootCompartment/(Km4 + EGFRub*rootCompartment)/rootCompartment;
end

Function_for_v4 is "Function for v4"

function ERK(ERKtot, pERK)
  ERKtot - pERK;
end

ERK is "ERK"

function Function_for_v6(PYK2m, kdeg6, rootCompartment)
  kdeg6*PYK2m*rootCompartment/rootCompartment;
end

Function_for_v6 is "Function for v6"

function EGFR(EGFRtot, pEGFR, EGFRub)
  EGFRtot - pEGFR - EGFRub;
end

EGFR is "EGFR"

function Function_for_v15(Km15, Vmax15, cMETm, rootCompartment)
  Vmax15*cMETm*rootCompartment/(Km15 + cMETm*rootCompartment)/rootCompartment;
end

Function_for_v15 is "Function for v15"

function Function_for_v3(EGFRtot, EGFRub, Ki3a, Ki3b, Km3, PF396, PYK2, Vmax3, kc3, pCbl, pEGFR, pPYK2, rootCompartment)
  ((Vmax3 + kc3*pCbl*rootCompartment)*EGFR(EGFRtot, pEGFR*rootCompartment, EGFRub*rootCompartment)/(Km3 + EGFR(EGFRtot, pEGFR*rootCompartment, EGFRub*rootCompartment)))*Ki3a/(Ki3a + PYK2tot(PYK2*rootCompartment, pPYK2*rootCompartment)/(1 + PF396/Ki3b))/rootCompartment;
end

Function_for_v3 is "Function for v3"

function Function_for_v1(EGF, EGFRtot, EGFRub, Gefitinib, Ki1, Km1, caEGF, kc1, pEGFR, rootCompartment)
  kc1*(EGF/(1 + Gefitinib/Ki1) + caEGF)*EGFR(EGFRtot, pEGFR*rootCompartment, EGFRub*rootCompartment)/(Km1 + EGFR(EGFRtot, pEGFR*rootCompartment, EGFRub*rootCompartment))/rootCompartment;
end

Function_for_v1 is "Function for v1"

function Function_for_v23(EMD, ERKtot, Ki23, Km23, kc23a, kc23b, pEGFR, pERK, pcMET, rootCompartment)
  (kc23a*pcMET*rootCompartment/(1 + EMD/Ki23) + kc23b*pEGFR*rootCompartment)*ERK(ERKtot, pERK*rootCompartment)/(Km23 + ERK(ERKtot, pERK*rootCompartment))/rootCompartment;
end

Function_for_v23 is "Function for v23"

function Function_for_v19(Cbltot, Km19, kc19, pCbl, pEGFR, rootCompartment)
  kc19*pEGFR*rootCompartment*Cbl(Cbltot, pCbl*rootCompartment)/(Km19 + Cbl(Cbltot, pCbl*rootCompartment))/rootCompartment;
end

Function_for_v19 is "Function for v19"


model *Shin_2018_EGFR_PYK2_c_Met_interaction_network_model()

  // Compartments and Species:
  compartment rootCompartment;
  species pEGFR in rootCompartment, EGFRub in rootCompartment, PYK2m in rootCompartment;
  species PYK2 in rootCompartment, pPYK2 in rootCompartment, pSTAT3 in rootCompartment;
  species cMETm in rootCompartment, cMET in rootCompartment, pcMET in rootCompartment;
  species pCbl in rootCompartment, aPTP in rootCompartment, pERK in rootCompartment;
  species STAT3uStattic in rootCompartment;

  // Assignment Rules:
  pSTAT3_norm := pSTAT3/ModelValue_77;
  pERK_norm := pERK/ModelValue_78;
  c_Met_norm := cMET/ModelValue_79;
  PYK2_norm := PYK2/ModelValue_80;

  // Reactions:
  v1:  => pEGFR; rootCompartment*Function_for_v1(EGF, EGFRtot, EGFRub, Gefitinib, Ki1, Km1, caEGF, kc1, pEGFR, rootCompartment);
  v2: pEGFR => ; rootCompartment*Function_for_v2(Km2, Vmax2, aPTP, kc2, pEGFR, rootCompartment);
  v3:  => EGFRub; rootCompartment*Function_for_v3(EGFRtot, EGFRub, Ki3a, Ki3b, Km3, PF396, PYK2, Vmax3, kc3, pCbl, pEGFR, pPYK2, rootCompartment);
  v4: EGFRub => ; rootCompartment*Function_for_v4(EGFRub, Km4, Vmax4, rootCompartment);
  v5:  => PYK2m; rootCompartment*Function_for_v5(Km5, Vmax5, Vs5, pSTAT3, rootCompartment);
  v6: PYK2m => ; rootCompartment*Function_for_v6(PYK2m, kdeg6, rootCompartment);
  v7:  => PYK2; rootCompartment*Function_for_v7(Km7, PYK2m, Vmax7, rootCompartment);
  v8: PYK2 => ; rootCompartment*Function_for_v8(PYK2, kdeg8, rootCompartment);
  v9: PYK2 => pPYK2; rootCompartment*Function_for_v9(EMD, Ki9, Km9, PYK2, kc9a, kc9b, pEGFR, pcMET, rootCompartment);
  v10: pPYK2 => PYK2; rootCompartment*Function_for_v10(Km10, Vmax10, aPTP, kc10, pPYK2, rootCompartment);
  v11:  => pSTAT3; rootCompartment*Function_for_v11(Ki3b, Km11, PF396, STAT3tot, STAT3uStattic, kc11, pPYK2, pSTAT3, rootCompartment);
  v12: pSTAT3 => ; rootCompartment*Function_for_v12(Km12, Vmax12, aPTP, kc12, pSTAT3, rootCompartment);
  v13:  => cMETm; rootCompartment*Function_for_v13(Km13, Vmax13, Vs13, pSTAT3, rootCompartment);
  v14: cMETm => ; rootCompartment*Function_for_v14(cMETm, kdeg14, rootCompartment);
  v15:  => cMET; rootCompartment*Function_for_v15(Km15, Vmax15, cMETm, rootCompartment);
  v16: cMET => ; rootCompartment*Function_for_v16(Km16, cMET, kc16, kdeg16, pCbl, rootCompartment);
  v17: cMET => pcMET; rootCompartment*Function_for_v17(HGF, Km17, cMET, caHGF, kc17, rootCompartment);
  v18: pcMET => cMET; rootCompartment*Function_for_v18(Km18, Vmax18, pcMET, rootCompartment);
  v19:  => pCbl; rootCompartment*Function_for_v19(Cbltot, Km19, kc19, pCbl, pEGFR, rootCompartment);
  v20: pCbl => ; rootCompartment*Function_for_v20(Km20, Vmax20, aPTP, kc20, pCbl, rootCompartment);
  v21:  => aPTP; rootCompartment*Function_for_v21(Km21, PTPtot, aPTP, kc21, pEGFR, rootCompartment);
  v22: aPTP => ; rootCompartment*Function_for_v22(Km22, Vmax22, aPTP, rootCompartment);
  v23:  => pERK; rootCompartment*Function_for_v23(EMD, ERKtot, Ki23, Km23, kc23a, kc23b, pEGFR, pERK, pcMET, rootCompartment);
  v24: pERK => ; rootCompartment*Function_for_v24(Km24, Vmax24, pERK, rootCompartment);
  v25:  => STAT3uStattic; rootCompartment*Function_for_v25(STAT3tot, STAT3uStattic, Stattictot, ka25, kd25, pSTAT3, rootCompartment);

  // Species initializations:
  pEGFR = 0.109014;
  EGFRub = 6.93991;
  PYK2m = 0.6219;
  PYK2 = 9.29922;
  pPYK2 = 2.51016;
  pSTAT3 = 1.17843;
  cMETm = 0.0228566;
  cMET = 4.67164;
  pcMET = 0.502111;
  pCbl = 10.4757;
  aPTP = 0.49418;
  pERK = 0.669043;
  STAT3uStattic = 0;

  // Compartment initializations:
  rootCompartment = 1;

  // Variable initializations:
  EGF = 10;
  HGF = 0;
  caSTAT3 = 0;
  kc1 = 413.048;
  Km1 = 248.886;
  kc2 = 1406.05;
  Km2 = 3.80189;
  Vmax3 = 0.000103753;
  Km3 = 2.2856;
  Ki3a = 0.0835603;
  Vmax4 = 11.1173;
  kc3 = 10.7895;
  Km4 = 90.7821;
  Vs5 = 26.5461;
  Vmax5 = 34.0408;
  Km5 = 4.74242;
  kdeg6 = 53.5797;
  Vmax7 = 3.34965;
  Km7 = 3.33426;
  kc9a = 0.463447;
  kc9b = 0.988553;
  Km9 = 34.914;
  Vmax10 = 0.530884;
  Km10 = 9.14113;
  kdeg8 = 0.0566239;
  kc11 = 0.321366;
  Km11 = 20.6063;
  kc12 = 0.000289734;
  Km12 = 11.5878;
  Vs13 = 0.0937562;
  Vmax13 = 0.354813;
  Km13 = 38.7258;
  kdeg14 = 4.56037;
  Vmax15 = 91.4113;
  Km15 = 6.45654;
  kc17 = 0.000810961;
  Km17 = 9.81748;
  Vmax18 = 0.0606736;
  Km18 = 9.95405;
  kdeg16 = 24.4906;
  kc16 = 1.1749;
  Km16 = 528.445;
  kc19 = 52.723;
  Km19 = 13.3045;
  kc20 = 35.6451;
  Km20 = 24.322;
  kc21 = 0.00397192;
  Km21 = 52.723;
  Vmax22 = 0.034914;
  Km22 = 46.4515;
  Vmax2 = 112.202;
  Vmax12 = 7.63836;
  Vmax20 = 0.0483059;
  kc23a = 7030720000;
  kc23b = 843335000;
  Km23 = 2.83139;
  Vmax24 = 4395420000;
  Km24 = 0.156675;
  kc10 = 0.00610942;
  Ki9 = 1.65577;
  Ki23 = 13.4896;
  ka25 = 127.35;
  kd25 = 11.749;
  kalEMD1 = 9311.08;
  caEGF = 0.0891251;
  caHGF = 0.0090365;
  EGFRtot = 398.107;
  STAT3tot = 144.212;
  Cbltot = 174.985;
  PTPtot = 296.483;
  ERKtot = 166.725;
  Ki1 = 1;
  Ki3b = 1;
  Gefitinib = 0;
  EMD = 0;
  PF396 = 0;
  Stattictot = 0;
  pSTAT3_max = 128;
  pERK_max = 163.6;
  c_Met_max = 16.7;
  PYK2_max = 14.58;
  ModelValue_77 = pSTAT3_max;
  ModelValue_78 = pERK_max;
  ModelValue_79 = c_Met_max;
  ModelValue_80 = PYK2_max;

  // Other declarations:
  var pSTAT3_norm, pERK_norm, c_Met_norm, PYK2_norm;
  const rootCompartment, EGF, HGF, caSTAT3, kc1, Km1, kc2, Km2, Vmax3, Km3;
  const Ki3a, Vmax4, kc3, Km4, Vs5, Vmax5, Km5, kdeg6, Vmax7, Km7, kc9a, kc9b;
  const Km9, Vmax10, Km10, kdeg8, kc11, Km11, kc12, Km12, Vs13, Vmax13, Km13;
  const kdeg14, Vmax15, Km15, kc17, Km17, Vmax18, Km18, kdeg16, kc16, Km16;
  const kc19, Km19, kc20, Km20, kc21, Km21, Vmax22, Km22, Vmax2, Vmax12, Vmax20;
  const kc23a, kc23b, Km23, Vmax24, Km24, kc10, Ki9, Ki23, ka25, kd25, kalEMD1;
  const caEGF, caHGF, EGFRtot, STAT3tot, Cbltot, PTPtot, ERKtot, Ki1, Ki3b;
  const Gefitinib, EMD, PF396, Stattictot, pSTAT3_max, pERK_max, c_Met_max;
  const PYK2_max, ModelValue_77, ModelValue_78, ModelValue_79, ModelValue_80;

  // Unit definitions:
  unit time_unit = 60 second;
  unit substance = 1e-9 mole;

  // Display Names:
  time_unit is "time";
  ModelValue_77 is "Initial for pSTAT3_max";
  ModelValue_78 is "Initial for pERK_max";
  c_Met_norm is "c-Met_norm";
  ModelValue_79 is "Initial for c_Met_max";
  ModelValue_80 is "Initial for PYK2_max";

  // SBO terms:
  v7.sboTerm = 184
  v15.sboTerm = 184

  // CV terms:
  rootCompartment hypernym "http://identifiers.org/cl/CL:0000000"
  pEGFR hypernym "http://identifiers.org/pr/PR:000006933"
  EGFRub hypernym "http://identifiers.org/pr/PR:000006933"
  EGFRub property "http://identifiers.org/pato/PATO:0002216"
  PYK2m property "http://identifiers.org/ncit/C17020"
  PYK2m property "http://identifiers.org/chebi/CHEBI:33699"
  PYK2 hypernym "http://identifiers.org/ncit/C17020"
  pPYK2 hypernym "http://identifiers.org/ncit/C17020"
  pSTAT3 hypernym "http://identifiers.org/pr/PR:000002089"
  cMETm property "http://identifiers.org/pr/PR:P08581"
  cMETm property "http://identifiers.org/chebi/CHEBI:33699"
  cMET hypernym "http://identifiers.org/pr/PR:P08581"
  pcMET hypernym "http://identifiers.org/pr/PR:P08581"
  pCbl hypernym "http://identifiers.org/ncit/C18547"
  aPTP hypernym "http://identifiers.org/ncit/C17444"
  pERK hypernym "http://identifiers.org/pr/PR:000000019"
  STAT3uStattic property "http://identifiers.org/pr/PR:000002089"
  STAT3uStattic property "http://identifiers.org/chebi/CHEBI:86989"
  v1 hypernym "http://identifiers.org/ncit/C18496"
  v2 hypernym "http://identifiers.org/ncit/C21018"
  v3 hypernym "http://identifiers.org/sbo/SBO:0000224"
  v4 hypernym "http://identifiers.org/go/GO:0016579"
  v5 hypernym "http://identifiers.org/sbo/SBO:0000183"
  v6 hypernym "http://identifiers.org/sbo/SBO:0000179"
  v7 identity "http://identifiers.org/sbo/SBO:0000184"
  v8 hypernym "http://identifiers.org/sbo/SBO:0000179"
  v9 hypernym "http://identifiers.org/ncit/C18496"
  v10 hypernym "http://identifiers.org/ncit/C21018"
  v11 hypernym "http://identifiers.org/ncit/C18496"
  v12 hypernym "http://identifiers.org/ncit/C21018"
  v13 hypernym "http://identifiers.org/sbo/SBO:0000183"
  v14 hypernym "http://identifiers.org/sbo/SBO:0000179"
  v15 identity "http://identifiers.org/sbo/SBO:0000184"
  v16 hypernym "http://identifiers.org/sbo/SBO:0000179"
  v17 hypernym "http://identifiers.org/ncit/C18496"
  v18 hypernym "http://identifiers.org/ncit/C21018"
  v19 hypernym "http://identifiers.org/ncit/C18496"
  v20 hypernym "http://identifiers.org/ncit/C21018"
  v21 hypernym "http://identifiers.org/ncit/C64382"
  v21 hypernym "http://identifiers.org/ncit/C16983"
  v22 hypernym "http://identifiers.org/ncit/C21018"
  v23 hypernym "http://identifiers.org/ncit/C18496"
  v24 hypernym "http://identifiers.org/ncit/C21018"
  v25 part "http://identifiers.org/chebi/CHEBI:86989"
  v25 hypernym "http://identifiers.org/go/GO:0008144"
end

Shin_2018_EGFR_PYK2_c_Met_interaction_network_model is "Shin_2018_EGFR-PYK2-c-Met interaction network_model"

Shin_2018_EGFR_PYK2_c_Met_interaction_network_model description "http://identifiers.org/pubmed/29920512"
Shin_2018_EGFR_PYK2_c_Met_interaction_network_model model_entity_is "http://identifiers.org/biomodels.db/MODEL1909270001",
                                                                    "http://identifiers.org/biomodels.db/BIOMD0000000826"
Shin_2018_EGFR_PYK2_c_Met_interaction_network_model property "http://identifiers.org/mamo/MAMO_0000046"
Shin_2018_EGFR_PYK2_c_Met_interaction_network_model property "http://identifiers.org/ncit/C71732"
Shin_2018_EGFR_PYK2_c_Met_interaction_network_model taxon "http://identifiers.org/taxonomy/9606"
