begin name
adlung1
end name

begin reactions
v1 {1.0}BaF3Epo = {1.0}$EXTERNAL
v18 {1.0}$EXTERNAL = {1.0}RpSHIP1
v19 {1.0}RpSHIP1 = {1.0}$EXTERNAL
v2 {1.0}$EXTERNAL = {1.0}pEpoR
v20 {1.0}$EXTERNAL = {1.0}PIP3
v21 {1.0}$EXTERNAL = {1.0}PIP3
v22 {1.0}PIP3 = {1.0}$EXTERNAL
v23 {1.0}PIP3 = {1.0}$EXTERNAL
v24 {1.0}PIP3 = {1.0}$EXTERNAL
v25 {1.0}PIP3 = {1.0}PIP3PDK1
v26 {1.0}PIP3PDK1 = {1.0}PIP3
v27 {1.0}PIP3 = {1.0}PIP3Akt
v28 {1.0}PIP3Akt = {1.0}PIP3
v29 {1.0}PIP3Akt = {1.0}$EXTERNAL
v3 {1.0}$EXTERNAL = {1.0}actPhosphatase
v30 {1.0}$EXTERNAL = {1.0}PIP3
v31 {1.0}$EXTERNAL = {1.0}pAkt
v32 {1.0}pAkt = {1.0}$EXTERNAL
v33 {1.0}$EXTERNAL = {1.0}PIP3
v34 {1.0}$EXTERNAL = {1.0}PIP3
v35 {1.0}$EXTERNAL = {1.0}pSos
v36 {1.0}pSos = {1.0}$EXTERNAL
v37 {1.0}$EXTERNAL = {1.0}RpSos
v38 {1.0}RpSos = {1.0}$EXTERNAL
v39 {1.0}RpSos = {1.0}pSos
v4 {1.0}actPhosphatase = {1.0}$EXTERNAL
v40 {1.0}$EXTERNAL = {1.0}GTPRas
v41 {1.0}$EXTERNAL = {1.0}GTPRas
v42 {1.0}GTPRas = {1.0}$EXTERNAL
v43 {1.0}$EXTERNAL = {1.0}pRaf
v44 {1.0}pRaf = {1.0}$EXTERNAL
v45 {1.0}$EXTERNAL = {1.0}pMek
v46 {1.0}pMek = {1.0}$EXTERNAL
v47 {1.0}pMek = {1.0}ppMek
v48 {1.0}ppMek = {1.0}pMek
v49 {1.0}$EXTERNAL = {1.0}pErk
v5 {1.0}pEpoR = {1.0}$EXTERNAL
v50 {1.0}pErk = {1.0}$EXTERNAL
v51 {1.0}pErk = {1.0}ppErk
v52 {1.0}ppErk = {1.0}pErk
v53 {1.0}$EXTERNAL = {1.0}Intperk
v54 {1.0}$EXTERNAL = {1.0}Intpakt
v55 {1.0}$EXTERNAL = {1.0}mTORa
v56 {1.0}$EXTERNAL = {1.0}mTORa
v57 {1.0}mTORa = {1.0}$EXTERNAL
v58 {1.0}mTORa = {1.0}TORC1
v59 {1.0}TORC1 = {1.0}mTORa
v6 {1.0}$EXTERNAL = {1.0}phos2
v60 {1.0}TORC1 = {1.0}$EXTERNAL
v61 {1.0}mTORa = {1.0}TORC2
v62 {1.0}TORC2 = {1.0}mTORa
v63 {1.0}TORC2 = {1.0}$EXTERNAL
v64 {1.0}$EXTERNAL = {1.0}RSKa
v65 {1.0}RSKa = {1.0}$EXTERNAL
v66 {1.0}$EXTERNAL = {1.0}pS6
v67 {1.0}$EXTERNAL = {1.0}pS6
v68 {1.0}$EXTERNAL = {1.0}pS6
v69 {1.0}pS6 = {1.0}$EXTERNAL
v7 {1.0}phos2 = {1.0}$EXTERNAL
v71 {1.0}$EXTERNAL = {1.0}IntpS6
v73 {1.0}$EXTERNAL = {1.0}Proliferation
end reactions

begin rate equations
v1 = Epodegradation*BaF3Epo[t]
v18 = kSHIP1*(pEpoR[t] - RpSHIP1[t])*(-RpSHIP1[t] + SHIP1tBaF3[t])
v19 = lSHIP1*RpSHIP1[t]
v2 = (EpoRactivation1*BaF3Epo[t]^nb*(EpoRBaF3[t] - (1 + kPI3K/(1 + kPI3K + kPI3K*kPI3Kras) + (kPI3K*kPI3Kras)/(1 + kPI3K + kPI3K*kPI3Kras))*pEpoR[t]))/((ksatb^nb + BaF3Epo[t]^nb)*(1 + phos2[t]/Ki1))
v20 = (kPI3K*vPIP3*pEpoR[t]*PI45P2BaF3[t])/(1 + kPI3K + kPI3K*kPI3Kras)
v21 = (kPI3K*kPI3Kras*main1*vPIP3*pEpoR[t]*PI45P2BaF3[t])/(1 + kPI3K + kPI3K*kPI3Kras)
v22 = kshbasal*PIP3[t]*(-RpSHIP1[t] + SHIP1tBaF3[t])
v23 = vPI45P2*PIP3[t]*PTENBaF3[t]
v24 = vPI34P2*PIP3[t]*RpSHIP1[t]
v25 = kPDK1*PIP3[t]*(PDK1tBaF3[t] - PIP3PDK1[t])
v26 = lPDK1*PIP3PDK1[t]
v27 = kAkt*PIP3[t]*(AkttBaF3[t] - pAkt[t] - PIP3Akt[t])
v28 = lAkt*PIP3Akt[t]
v29 = vpAkt*PIP3Akt[t]*PIP3PDK1[t]
v3 = Phosphataseactivation1*pEpoR[t]*(-actPhosphatase[t] + PhosphatasetBaF3[t])
v30 = vpAkt*PIP3Akt[t]*PIP3PDK1[t]
v31 = (vpAkt*PIP3Akt[t]*PIP3PDK1[t])/(1 + Aktin*kaktinb)
v32 = dpAkt*pAkt[t]
v33 = vPIP3basal*(-((kPI3K*pEpoR[t])/(1 + kPI3K + kPI3K*kPI3Kras)) - (kPI3K*kPI3Kras*pEpoR[t])/(1 + kPI3K + kPI3K*kPI3Kras) + PI3KtBaF3[t])*PI45P2BaF3[t]
v34 = main1*vPIP3basal*PI45P2BaF3[t]
v35 = kpes*ppErk[t]*(Sostb - pSos[t] - RpSos[t])
v36 = kdpes*pSos[t]
v37 = kSos*(pEpoR[t] - RpSos[t])*(Sostb - pSos[t] - RpSos[t])
v38 = lSos*RpSos[t]
v39 = kpes*ppErk[t]*RpSos[t]
v4 = Phosphatasedeactivation1*actPhosphatase[t]
v40 = kbackRas*(-GTPRas[t] - (kPI3K*kPI3Kras*pEpoR[t])/(1 + kPI3K + kPI3K*kPI3Kras) + RastBaF3[t])
v41 = kaRas*(-GTPRas[t] - (kPI3K*kPI3Kras*pEpoR[t])/(1 + kPI3K + kPI3K*kPI3Kras) + RastBaF3[t])*RpSos[t]
v42 = kdRas*GTPRas[t]
v43 = kpRaf*(GTPRas[t] + (kPI3K*kPI3Kras*pEpoR[t])/(1 + kPI3K + kPI3K*kPI3Kras))*(-pRaf[t] + RaftBaF3[t])
v44 = lpRaf*pRaf[t]
v45 = kpMek*(MektBaF3[t] - pMek[t] - ppMek[t])*pRaf[t]
v46 = lpMek*pMek[t]
v47 = kppMek*pMek[t]*pRaf[t]
v48 = lppMek*ppMek[t]
v49 = kpErk*(ErktBaF3[t] - pErk[t] - ppErk[t])*ppMek[t]
v5 = pEpoRdeactivation1*actPhosphatase[t]*pEpoR[t]
v50 = bDUSP3*lpErk*pErk[t]
v51 = (kppErk*pErk[t]*ppMek[t])/(1 + kmekinb*Mekin)
v52 = bDUSP3*lppErk*ppErk[t]
v53 = ppErk[t]
v54 = pAkt[t]
v55 = kvpakt*pAkt[t]*(-mTORa[t] + mTORt[t] - TORC1[t] - TORC2[t])
v56 = (kvppErk*RSKa[t]*(-mTORa[t] + mTORt[t] - TORC1[t] - TORC2[t]))/(1 + kinrskb*RSKin)
v57 = kdactm*mTORa[t]
v58 = (kst1*(Raptorb[t] - TORC1[t])*(mTORa[t] - TORC1[t] - TORC2[t]))/(1 + kinrapab*Rapamycin)
v59 = kdt1*TORC1[t]
v6 = (Phosact1*pEpoR[t]^n1)/(Ji1^n1 + pEpoR[t]^n1)
v60 = kdactm*TORC1[t]
v61 = kst2*(Rictorb[t] - TORC2[t])*(mTORa[t] - TORC1[t] - TORC2[t])
v62 = kdt2*TORC2[t]
v63 = kdactm*TORC2[t]
v64 = (karsk*ppErk[t]*(-RSKa[t] + RSKtb[t]))/(1 + kinrskb*RSKin)
v65 = kdrsk*RSKa[t]
v66 = kas6t*(-pS6[t] + S6tBaF3[t])*TORC1[t]
v67 = kas6r*RSKa[t]*(-pS6[t] + S6tBaF3[t])
v68 = kbacks6*(-pS6[t] + S6tBaF3[t])
v69 = kdphoss6*pS6[t]
v7 = Phosdeact1*phos2[t]
v71 = pS6[t]
v73 = pboffcorrect/60 + (pbk2correct*(cycleaktinb*pAkt[t] + cyclemekinb*ppErk[t]))/maxccb
end rate equations

begin parameters
Aktin = 0.0
EpoRactivation1 = 0.140964
Epodegradation = 0.0173287
Ji1 = 0.220505
Ki1 = 0.0272784
Mekin = 0.0
Phosact1 = 341.317
Phosdeact1 = "1e-05"
Phosphataseactivation1 = 144.425
Phosphatasedeactivation1 = "1e-05"
RSKin = 0.0
Rapamycin = 0.0
Sostb = "4.46181e-05"
bDUSP3 = 96.7699
cycleaktinb = 0.967522
cyclemekinb = 0.127989
dpAkt = 3.4739
initAkttBaF3 = 0.51
initErktBaF3 = 2.964
initMektBaF3 = 4.38
initPDK1tBaF3 = 0.763
initPI3KtBaF3 = 0.0124
initPI45P2BaF3 = 10.0
initPTENBaF3 = 0.1074
initRSKtb = 3.0306
initRaftBaF3 = 3.886
initRastBaF3 = 9.531
initRpSHIP1 = 0.0
initS6tBaF3 = 2.59
initSHIP1tBaF3 = 0.0842
initTORC1 = 0.0
kAkt = 9984.96
kPDK1 = 9439.5
kPI3K = 0.000104741
kPI3Kras = 10000.0
kSHIP1 = 0.0745937
kSos = 59.4049
kaRas = 2981.53
kaktinb = 1.866219406
karsk = 1.26435
kas6r = 0.000533083
kas6t = 2180.44
kbackRas = 0.0103384
kbacks6 = "1.00003e-05"
kdRas = 0.540777
kdactm = 0.0617342
kdpes = 0.0270729
kdphoss6 = 0.328006
kdrsk = 0.677229
kdt1 = 1588.13
kdt2 = "1e-05"
kinrapab = 2.778901656
kinrskb = 0.552054462
kmekinb = 3.224998336
kpErk = 9999.08
kpMek = 9774.26
kpRaf = 1.17959
kpes = 0.583255
kppErk = 9999.96
kppMek = 9999.77
ksatb = 0.0024577
kshbasal = "1e-05"
kst1 = 20.0908
kst2 = 0.0619403
kvpakt = 0.000174996
kvppErk = 0.000282332
lAkt = 10.1007
lPDK1 = 2355.54
lSHIP1 = 0.000650697
lSos = 0.39616
lpErk = 177.216
lpMek = 0.0414313
lpRaf = 2549.69
lppErk = 3.2516
lppMek = 1336.21
main1 = 0.000224787
maxccb = 0.99
n1 = 4.0
nb = 2.03939
pEpoRdeactivation1 = 3.20488
pbk2correct = 0.485791
pboffcorrect = 0.470245
vPI34P2 = 9996.96
vPI45P2 = 84.5564
vPIP3 = 10000.0
vPIP3basal = 0.104429
vpAkt = 6.90774
cyt = 1.0
end parameters

begin initial conditions
AkttBaF3[0] = AkttBaF3i
BaF3Epo[0] = BaF3Epoi
EpoRBaF3[0] = EpoRBaF3i
ErktBaF3[0] = ErktBaF3i
GTPRas[0] = GTPRasi
IntpS6[0] = IntpS6i
Intpakt[0] = Intpakti
Intperk[0] = Intperki
MektBaF3[0] = MektBaF3i
PDK1tBaF3[0] = PDK1tBaF3i
PI3KtBaF3[0] = PI3KtBaF3i
PI45P2BaF3[0] = PI45P2BaF3i
PIP3[0] = PIP3i
PIP3Akt[0] = PIP3Akti
PIP3PDK1[0] = PIP3PDK1i
PTENBaF3[0] = PTENBaF3i
PhosphatasetBaF3[0] = PhosphatasetBaF3i
Proliferation[0] = Proliferationi
RSKa[0] = RSKai
RSKtb[0] = RSKtbi
RaftBaF3[0] = RaftBaF3i
Raptorb[0] = Raptorbi
RastBaF3[0] = RastBaF3i
Rictorb[0] = Rictorbi
RpSHIP1[0] = RpSHIP1i
RpSos[0] = RpSosi
S6tBaF3[0] = S6tBaF3i
SHIP1tBaF3[0] = SHIP1tBaF3i
TORC1[0] = TORC1i
TORC2[0] = TORC2i
actPhosphatase[0] = actPhosphatasei
mTORa[0] = mTORai
mTORt[0] = mTORti
pAkt[0] = pAkti
pEpoR[0] = pEpoRi
pErk[0] = pErki
pMek[0] = pMeki
pRaf[0] = pRafi
pS6[0] = pS6i
pSos[0] = pSosi
phos2[0] = phos2i
ppErk[0] = ppErki
ppMek[0] = ppMeki
end initial conditions

begin initial values
AkttBaF3i = 0.51
BaF3Epoi = 0.002
EpoRBaF3i = 0.01862
ErktBaF3i = 2.964
GTPRasi = 0.17879248230044018
IntpS6i = 0.0
Intpakti = 0.0
Intperki = 0.0
MektBaF3i = 4.38
PDK1tBaF3i = 0.763
PI3KtBaF3i = 0.0124
PI45P2BaF3i = 10
PIP3i = 0.0014259096174786036
PIP3Akti = 0.296484152509495
PIP3PDK1i = 0.004335113669239996
PTENBaF3i = 0.1074
PhosphatasetBaF3i = 0.0415
Proliferationi = 0.0
RSKai = 0.06843365642650674
RSKtbi = 3.0306
RaftBaF3i = 3.886
Raptorbi = 0.1
RastBaF3i = 9.531
Rictorbi = 1.2329
RpSHIP1i = 0
RpSosi = 0.0
S6tBaF3i = 2.59
SHIP1tBaF3i = 0.0842
TORC1i = 0
TORC2i = 0.0
actPhosphatasei = 0.0
mTORai = 0.0
mTORti = 0.1
pAkti = 0.0025557633868391167
pEpoRi = 0.0
pErki = 0.017777899006355905
pMeki = 4.312731699382008
pRafi = 0.00032128827441495054
pS6i = 0.0003669720694067856
pSosi = 0.0
phos2i = 0.0
ppErki = 0.005858735624008178
ppMeki = 0.010369614478384468
end initial values

begin assignment rules
pS6plot := 412.8573*pS6[t]
end assignment rules

begin function definitions
end function definitions

begin events
end events

begin process annotations
end process annotations

begin species annotations
end species annotations

begin units
end units