// Created by libAntimony v2.13.0
function Function_for_PI3K_activation_deactivation_1(PI3K, aIRS, aPI3K, aRTK, k2f, k2fa, k2r)
  (k2f*aIRS + k2fa*aRTK)*PI3K - k2r*aPI3K;
end

Function_for_PI3K_activation_deactivation_1 is "Function for PI3K activation/deactivation_1"

function Function_for_mass_action_with_modifier_1(Akt, aAkt, aPI3K, k3f, k3r)
  k3f*Akt*aPI3K - k3r*aAkt;
end

Function_for_mass_action_with_modifier_1 is "Function for mass action with modifier_1"

function Function_for_mTOC1_acivation_deactivation_1(aAkt, amTORC1, k4f, k4r, mTORC1)
  k4f*mTORC1*aAkt - k4r*amTORC1;
end

Function_for_mTOC1_acivation_deactivation_1 is "Function for mTOC1 acivation/deactivation_1"

function Function_for_S6K_activation_deactivation_1(S6K, aS6K, amTORC1, k5f, k5r)
  k5f*S6K*amTORC1 - k5r*aS6K;
end

Function_for_S6K_activation_deactivation_1 is "Function for S6K activation/deactivation_1"

function Function_for_mass_action_with_modifier_2(IRS, aS6K, iIRS, k6f, k6r)
  k6f*IRS*aS6K - k6r*iIRS;
end

Function_for_mass_action_with_modifier_2 is "Function for mass action with modifier_2"

function Function_for_RTK_activation_deactivation_1(FOXO, RTK, aRTK, k7f, k7fa, k7r)
  (k7f + k7fa*FOXO)*RTK - k7r*aRTK;
end

Function_for_RTK_activation_deactivation_1 is "Function for RTK activation/deactivation_1"

function Function_for_mass_action_with_modifier_3(RasGDP, RasGTP, aRTK, k8f, k8r)
  k8f*RasGDP*aRTK - k8r*RasGTP;
end

Function_for_mass_action_with_modifier_3 is "Function for mass action with modifier_3"

function Function_for_mass_action_with_modifier_4(Raf, RasGTP, aRaf, k9f, k9r)
  k9f*Raf*RasGTP - k9r*aRaf;
end

Function_for_mass_action_with_modifier_4 is "Function for mass action with modifier_4"

function Function_for_mass_action_with_modifier_5(MEK, aMEK, aRaf, k10f, k10r)
  k10f*MEK*aRaf - k10r*aMEK;
end

Function_for_mass_action_with_modifier_5 is "Function for mass action with modifier_5"

function Function_for_mass_action_with_modifier_6(ERK, aERK, aMEK, k11f, k11r)
  k11f*ERK*aMEK - k11r*aERK;
end

Function_for_mass_action_with_modifier_6 is "Function for mass action with modifier_6"

function Function_for_mass_action_with_modifier_7(Raf, aERK, iRaf, k12f, k12r)
  k12f*Raf*aERK - k12r*iRaf;
end

Function_for_mass_action_with_modifier_7 is "Function for mass action with modifier_7"

function Function_for_mass_action_with_modifier_8(RTK, aERK, iRTK, k13f, k13r)
  k13f*RTK*aERK - k13r*iRTK;
end

Function_for_mass_action_with_modifier_8 is "Function for mass action with modifier_8"

function Function_for_mass_action_with_modifier_9(FOXO, aAkt, iFOXO, k14f, k14r)
  k14f*FOXO*aAkt - k14r*iFOXO;
end

Function_for_mass_action_with_modifier_9 is "Function for mass action with modifier_9"


model *Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics()

  // Compartments and Species:
  compartment compartment_;
  species IRS in compartment_, aIRS in compartment_, iIRS in compartment_;
  species PI3K in compartment_, aPI3K in compartment_, Akt in compartment_;
  species aAkt in compartment_, mTORC1 in compartment_, amTORC1 in compartment_;
  species S6K in compartment_, aS6K in compartment_, FOXO in compartment_;
  species iFOXO in compartment_, RTK in compartment_, aRTK in compartment_;
  species iRTK in compartment_, RasGDP in compartment_, RasGTP in compartment_;
  species Raf in compartment_, aRaf in compartment_, iRaf in compartment_;
  species MEK in compartment_, aMEK in compartment_, ERK in compartment_;
  species aERK in compartment_, AktI in compartment_, iAkt in compartment_;
  species MEKI in compartment_, iMEK in compartment_;

  // Reactions:
  IRS__activation_deactivation: IRS -> aIRS; compartment_*(k1f*IRS - k1r*aIRS);
  PI3K_activation_deactivation: PI3K -> aPI3K; compartment_*Function_for_PI3K_activation_deactivation_1(PI3K, aIRS, aPI3K, aRTK, k2f, k2fa, k2r);
  Akt_activation_deactivation: Akt -> aAkt; compartment_*Function_for_mass_action_with_modifier_1(Akt, aAkt, aPI3K, k3f, k3r);
  mTOC1_acivation_deactivation: mTORC1 -> amTORC1; compartment_*Function_for_mTOC1_acivation_deactivation_1(aAkt, amTORC1, k4f, k4r, mTORC1);
  S6K_activation_deactivation: S6K -> aS6K; compartment_*Function_for_S6K_activation_deactivation_1(S6K, aS6K, amTORC1, k5f, k5r);
  IRS_inhibition: IRS => iIRS; compartment_*Function_for_mass_action_with_modifier_2(IRS, aS6K, iIRS, k6f, k6r);
  RTK_activation_deactivation: RTK -> aRTK; compartment_*Function_for_RTK_activation_deactivation_1(FOXO, RTK, aRTK, k7f, k7fa, k7r);
  RasGDP__activation_deactivation: RasGDP -> RasGTP; compartment_*Function_for_mass_action_with_modifier_3(RasGDP, RasGTP, aRTK, k8f, k8r);
  Raf_activation_deactivation: Raf -> aRaf; compartment_*Function_for_mass_action_with_modifier_4(Raf, RasGTP, aRaf, k9f, k9r);
  MEK_activation_deactivation: MEK -> aMEK; compartment_*Function_for_mass_action_with_modifier_5(MEK, aMEK, aRaf, k10f, k10r);
  ERK_activation_deactivation: ERK -> aERK; compartment_*Function_for_mass_action_with_modifier_6(ERK, aERK, aMEK, k11f, k11r);
  Raf_inhibition: Raf -> iRaf; compartment_*Function_for_mass_action_with_modifier_7(Raf, aERK, iRaf, k12f, k12r);
  RTK_inhibition: RTK -> iRTK; compartment_*Function_for_mass_action_with_modifier_8(RTK, aERK, iRTK, k13f, k13r);
  FOXO_inhibition: FOXO -> iFOXO; compartment_*Function_for_mass_action_with_modifier_9(FOXO, aAkt, iFOXO, k14f, k14r);
  Akt_inhibition: Akt + AktI -> iAkt; compartment_*(k15f*Akt*AktI - k15r*iAkt);
  MEK_inhibition: MEK + MEKI -> iMEK; compartment_*(k16f*MEK*MEKI - k16r*iMEK);

  // Species initializations:
  IRS = 100;
  aIRS = 0;
  iIRS = 0;
  PI3K = 100;
  aPI3K = 0;
  Akt = 100;
  aAkt = 0;
  mTORC1 = 299.999999999999;
  amTORC1 = 0;
  S6K = 299.999999999999;
  aS6K = 0;
  FOXO = 200;
  iFOXO = 0;
  RTK = 200;
  aRTK = 0;
  iRTK = 0;
  RasGDP = 100;
  RasGTP = 0;
  Raf = 100;
  aRaf = 0;
  iRaf = 0;
  MEK = 299.999999999999;
  aMEK = 0;
  ERK = 899.999999999996;
  aERK = 0;
  AktI = 0;
  iAkt = 0;
  MEKI = 0;
  iMEK = 0;

  // Compartment initializations:
  compartment_ = 1;

  // Variable initializations:
  k1f = 0.01;
  k1r = 0.01;
  k2f = 0.001;
  k2fa = 0.001;
  k2r = 0.01;
  k3f = 0.001;
  k3r = 0.01;
  k4f = 0.001;
  k4r = 0.01;
  k5f = 0.001;
  k5r = 0.01;
  k6f = 0.1;
  k6r = 0.001;
  k7f = 0.01;
  k7fa = 0.01;
  k7r = 0.01;
  k8f = 0.001;
  k8r = 0.01;
  k9f = 0.001;
  k9r = 0.01;
  k10f = 0.001;
  k10r = 0.01;
  k11f = 0.001;
  k11r = 0.01;
  k12f = 0.01;
  k12r = 0.001;
  k13f = 0.1;
  k13r = 0.001;
  k14f = 0.1;
  k14r = 0.001;
  k15f = 0.01;
  k15r = 0.001;
  k16f = 0.01;
  k16r = 0.001;

  // Other declarations:
  const compartment_, k1f, k1r, k2f, k2fa, k2r, k3f, k3r, k4f, k4r, k5f, k5r;
  const k6f, k6r, k7f, k7fa, k7r, k8f, k8r, k9f, k9r, k10f, k10r, k11f, k11r;
  const k12f, k12r, k13f, k13r, k14f, k14r, k15f, k15r, k16f, k16r;

  // Unit definitions:
  unit volume = 1e-3 litre;
  unit substance = 1e-3 mole;

  // Display Names:
  compartment_ is "compartment";
  IRS__activation_deactivation is "IRS  activation/deactivation";
  PI3K_activation_deactivation is "PI3K activation/deactivation";
  Akt_activation_deactivation is "Akt activation/deactivation";
  mTOC1_acivation_deactivation is "mTOC1 acivation/deactivation";
  S6K_activation_deactivation is "S6K activation/deactivation";
  IRS_inhibition is "IRS inhibition";
  RTK_activation_deactivation is "RTK activation/deactivation";
  RasGDP__activation_deactivation is "RasGDP  activation/deactivation";
  Raf_activation_deactivation is "Raf activation/deactivation";
  MEK_activation_deactivation is "MEK activation/deactivation";
  ERK_activation_deactivation is "ERK activation/deactivation";
  Raf_inhibition is "Raf inhibition";
  RTK_inhibition is "RTK inhibition";
  FOXO_inhibition is "FOXO inhibition";
  Akt_inhibition is "Akt inhibition";
  MEK_inhibition is "MEK inhibition";

  // CV terms:
  IRS hypernym "http://identifiers.org/uniprot/P35568"
  aIRS hypernym "http://identifiers.org/uniprot/P35568"
  iIRS hypernym "urn:miriam:sbo:SBO%3A0000015"
  PI3K hypernym "urn:miriam:uniprot:C17270"
  aPI3K hypernym "http://identifiers.org/ncit/C17270"
  Akt hypernym "http://identifiers.org/uniprot/P31749"
  aAkt hypernym "http://identifiers.org/uniprot/P31749"
  mTORC1 hypernym "http://identifiers.org/uniprot/P42345"
  amTORC1 encoder "http://identifiers.org/uniprot/P42345"
  S6K hypernym "http://identifiers.org/uniprot/P23443"
  aS6K hypernym "http://identifiers.org/uniprot/P23443"
  FOXO hypernym "http://identifiers.org/uniprot/Q12778"
  iFOXO hypernym "http://identifiers.org/uniprot/Q12778"
  RTK hypernym "http://identifiers.org/uniprot/Q08345"
  aRTK hypernym "http://identifiers.org/uniprot/Q08345"
  iRTK hypernym "http://identifiers.org/uniprot/Q08345"
  RasGDP hypernym "http://identifiers.org/uniprot/P01112"
  RasGTP hypernym "http://identifiers.org/uniprot/P01112"
  Raf hypernym "http://identifiers.org/uniprot/P04049"
  aRaf hypernym "http://identifiers.org/uniprot/P04049"
  iRaf hypernym "http://identifiers.org/uniprot/P04049"
  MEK hypernym "http://identifiers.org/uniprot/Q02750"
  aMEK hypernym "http://identifiers.org/uniprot/Q02750"
  ERK hypernym "http://identifiers.org/uniprot/P27361"
  aERK hypernym "http://identifiers.org/uniprot/P27361"
  AktI property "http://identifiers.org/chebi/CHEBI:35222"
  iAkt hypernym "http://identifiers.org/uniprot/P31749"
  MEKI property "http://identifiers.org/chebi/CHEBI:35222"
  iMEK hypernym "http://identifiers.org/uniprot/Q02750"
end

Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics is "Nguyen2016 - Feedback regulation in cell signalling: Lessons for cancer therapeutics"

Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics model_entity_is "http://identifiers.org/biomodels.db/MODEL1708250003"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics model_entity_is "http://identifiers.org/biomodels.db/BIOMD0000000651"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics description "http://identifiers.org/pubmed/26481970"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics model_entity_is "http://identifiers.org/biomodels.db/BIOMD0000000651",
                                                                                                     "http://identifiers.org/biomodels.db/MODEL1708250003"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics description "http://identifiers.org/pubmed/26481970"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics taxon "http://identifiers.org/taxonomy/9606"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics property "http://identifiers.org/mamo/MAMO_0000046"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics property "http://identifiers.org/ncit/C16212"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics part "http://identifiers.org/pw/PW:0000102"
Nguyen2016___Feedback_regulation_in_cell_signalling__Lessons_for_cancer_therapeutics part "http://identifiers.org/pw/PW:0000180"
