Supplementary figure 1

0 1 5 10 500.0

0.2

0.4

0.6

0.8

1.0

1.2NF90.8T265-2C

sNF96.2

bortezomib (nM)

Rel

ativ

e lu

min

esce

nce

(a.u

.)

0 1 2 3 40.0

2.5

5.0

16 Gy

Control4 Gy8 Gy12 Gy

Time (days)

Flou

resc

ence

inte

nsity

(104 )

sNF96.2

0 1 2 3 40

4

8Control4 Gy8 Gy12 Gy16 Gy

Time (days)

Flou

resc

ence

inte

nsity

(104 )

T265-2C

0 1 2 3 40

5

10 Control4 Gy8 Gy12 Gy16 Gy

Time (days)

Flou

resc

ence

inte

nsity

(104 )

0 1 2 3 40.0

3.5

7.0Control4 Gy8 Gy12 Gy16 Gy

Time (days)

Flou

resc

ence

inte

nsity

(104 )

ST88-14

NF90.8

Supplementary figure 2

sNF96.2

T265-2C ST88-14

NF90.8

Supplementary figure 3

72 960.0

4.5

9.0

Control12 Gyrapamycinrapamycin + 12 Gyeverolimuseverolimus + 12 Gy

******

*********

***

### ### ### ###

Time (h)

Flou

resc

ence

inte

nsity

(104 )

T265-2C

ST88-14

NF90.8

siRNA G

FPsiR

NA mTO

R#13

siRNA m

TOR#

19

mTOR

GAPDH

mTOR

GAPDH

siRNA G

FPsiR

NA mTO

R#13

siRNA m

TOR#

19

mTOR

GAPDH

siRNA G

FPsiR

NA mTO

R#13

siRNA m

TOR#

19A

Supplementary figure 4

72 960

2

4

6

8

****** *********

***

### ######

###

Time (h)

Flou

resc

ence

inte

nsity

(104 )

72 960

4

8

12

siRNA GFPsiRNA GFP + 12 GysiRNA mTOR#13siRNA mTOR#13 + 12 GysiRNA mTOR#19siRNA mTOR#19 + 12 Gy

****** *** ***

*** ***

### ###

######

Time (h)

Flou

resc

ence

inte

nsity

(104 )

72 960

4

8

12

****** *** ***

*** ***

######

######

Time (h)

Flou

resc

ence

inte

nsity

(104 )

B

1 2 3 4 5 6 7 8 9 1011121314151617181912

16

20

24

Control

bortezomib (0.65 mg/m2) + everolimusbortezomib (0.95 mg/m2) + everolimusbortezomib (1.3 mg/m2) + everolimus

Days

Bod

y m

ass

(g)

Supplementary figure 5

CompoundMolecular

weight CompoundMolecular

weightNalbuphine 393.91 ETHYNYLESTRADIOL 296.41Raclopride 347.24 2(1H)-Pyrimidinone 243.22Zacopride 364.27 L-Glutamic acid 508.49SKF 83566 413.15 TFMPP 266.693'-deoxydenosine 255.75 Pramipexole 211.33AM 404 395.59 LIDOCAINE 234.34PILOCARPINE HYDROCHLORIDE 244.72 Indomethacin 362.30NIFEDIPINE 346.34 LY 171883 318.38CPD000042823 244.27 Paroxetine 445.443-HYDROXY-1,2-DIMETHYL-4(1H)-PYRIDONE 139.15 Epigallocatechin gallate 458.38LOXAPINE SUCCINATE 445.90 5-Amino-2-hydroxy-benzoic acid 153.14d-3-Methoxy-N-methylmorphinan hydrobromide 370.33 Oxiranecarboxylic acid 326.82Duloxetine 297.42 Cephalexin monohydrate 347.39Glycine, N-[2-[(acetylthio)methyl]-1-oxo-3-phenylpropyl]-,phenylmethyl ester 385.48 PIDOTIMOD 244.27Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-, monosodium salt 318.14 RAMIPRIL 416.52PROGESTERONE 314.47 LEVOFLOXACIN 361.37FAMOTIDINE 337.43 19-Nortestosterone 274.40SR 57,227A 248.16 NIZATIDINE 331.45Pancuronium 732.68 5-FLUOROCYTOSINE 129.09METRONIDAZOLE 171.16 Trileptal 252.27Benzeneacetic acid 438.32 TROXIPIDE 294.35Benzeneacetonitrile 500.08 ACTARIT 193.20Benzeneethanamine, N,Alpha-dimethyl-N-2-propynyl-(R) 223.75 AZELASTINE HCl 418.37Capsaicin 305.42 TOCAINIDE 192.26SALBUTAMOL SULFATE 288.36 TAXIFOLIN-(+/-) 304.26(±)-Vesamicol hydrochloride 295.85 FENPIVERINIUM BROMIDE 417.39Picrotin - Picrotoxinin 602.59 CEFATRIZINE PROPYLENE GLYCOL 538.59Terazosin 459.93 IDEBENONE 338.45diphenylcyclopropenone 206.24 LEVOSULPIRIDE 341.434-Thiazolidinecarboxylic acid, 2-oxo-, (R) 147.15 Pemoline 176.18Mesoridazine 544.74 LETROZOL 285.313(2H)-Pyridazinone, 6-[4-(difluoromethoxy)-3-methoxyphenyl] 268.22 MEROPENEM 383.4610H-Phenothiazine, 2-chloro-10-[3-(4-methyl-1-piperazinyl)propyl 606.09 ORLISTAT 495.751H-Cyclopenta[b]quinolin-9-amine, 2,3,5,6,7,8-hexahydro-, monohydrochloride 188.27 ONDANSETRON HCl 329.83CLOTRIMAZOLE 344.84 LEVONORGESTREL 312.45LORATADINE 382.89 CETRAXATE HCl 341.84PHENELZINE SULFATE SALT 234.28 Alprazolam 308.77Riluzole 270.66 LAMOTRIGINE 256.09Naltrindole 477.99 CROTAMITON 203.29Nornicotine 148.21 AMFEBUTAMONE HCl 239.75Bifemelane 305.85 ALFUZOSIN 389.46CGS 15943 285.69 Amisulpride 369.48Cinanserin 381.45 LOFEPRAMINE 455.43Cisapride 483.97 PEROSPIRONE HCl 463.04Indatraline 328.67 DOCETAXEL 807.90TRAZODONE HYDROCHLORIDE 408.33 HONOKIOL 266.34 Prazosin 433.38 TOLTERODINE TARTRATE 475.58URAPIDIL HYDROCHLORIDE 423.94 CARMOFUR 257.27(-)-Cotinine 176.22 METHYL PAROXETINE 343.40D-CYCLOSERINE 102.09 OLMESARTAN MEDOXOMIL 446.51Fluvoxamine 434.41 LOSARTAN Potassium 461.01Doxepin 315.84 TEMOZOLOMIDE 194.15TRIFLUOPERAZINE DIHYDROCHLORIDE 480.42 Methyltestosterone 302.46(+)-3-HYDROXY-N-METHYLMORPHINAN D-TARTRATE 407.47 TOSUFLOXACIN TOSYLATE 576.55L-Ornithine 248.28 MECILLINAM 325.43Maprotilline HCl 313.87 ATOMEXETINE HCl 291.82Pizotyline 411.52 ARTESUNATE 384.43BETA-ESTRADIOL 272.39 ITRACONAZOLE 705.65N,N'-DIACETYL-1,6-DIAMINOHEXANE 200.28 CEFPODOXIME PROXETIL 557.60DIPHENHYDRAMINE HYDROCHLORIDE 291.82 BUFLOMEDIL HYDROCHLORIDE 343.85Galanthamine 368.27 4-Chloro-N-(2-morpholin-4-yl-ethyl)-benzamide 268.74Ifenprodil 409.50 HALOMETASONE MONOHYDRATE 444.90TETRAETHYLTHIURAM DISULFIDE 296.52 TRICLABENDAZOLE 359.66Piribedil 343.81 ROFECOXIB 314.36KETOCONAZOLE 531.44 BISOPROLOL FUMARATE 383.49TRIPELENNAMINE HYDROCHLORIDE 291.83 EZETIMIBE 409.43Pyrazinecarboxamide, 3,5-diamino-N-(aminoiminomethyl)-6-chloro 302.12 TIAGABINE HCl 412.019-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE 234.73 IDARUBICIN HCl 533.96CLARITHROMYCIN 747.97 FLUBENDAZOLE 313.29ARIPIPRAZOLE 448.39 TACROLIMUS 804.04

Supplementary Table 1

TRIMEBUTINE MALEATE 503.55 VALACICLOVIR HYDROCHLORIDE 360.80Mestanolone 304.47 ROXATIDINE ACETATE HCl 384.90NISOLDIPINE 388.42 DEXBROMPHENIRAMINE MALEATE 435.32PICEID 390.39 ANAGRELIDE HCl 292.551-(2-Methyl-5-nitro-imidazol-1-yl)-propan-2-ol 185.18 TEGASEROD MALEATE 417.46NIFEKALANT HCl 441.92 MILRINONE 211.22NATEGLINIDE 317.43 LEVOCETIRIZINE 388.90MEGESTROL ACETATE 384.52 Citalopram hydrobromide 405.31ORMETOPRIM 274.32 TICLOPIDINE HCl 300.25ZILEUTON 236.29 LOXOPROFEN SODIUM 268.29STAVUDINE 224.22 ZAFIRLUKAST 575.68GABEXATE MESYLATE 417.48 TERBINAFINE HCl 327.90OXICONAZOLE NITRATE 492.15 ISRADIPINE 371.39KITASAMYCIN 828.01 VALSARTAN 435.53FAMCICLOVIR 321.34 Piroxicam 335.85(±)-Sotalol hydrochloride 308.82 GLYCOPYRROLATE 398.34RUFLOXACIN HCl 363.41 Physostigmine 324.39TAXIFOLIN-(+) 304.26 LOBELINE HYDROCHLORIDE 373.92ALOSETRON HCl 330.82 DOXYLAMINE SUCCINATE 388.46BUPROPION HYDROCHLORIDE 276.21 Milnacipran 282.81IRSOGLADINE MALEATE 372.17 5-fluoro-2-pyrimidone 114.08ACARBOSE 645.61 Chlorpheniramine 390.87BENPROPERINE PHOSPHATE 407.45 DOFETILIDE 441.56PHENPROBAMATE 179.22 FORMOTEROL FUMARATE DIHYDRATE 496.51MEMANTINE HYDROCHLORIDE 215.77 RIZATRIPTAN BENZOATE 391.47Carvedilol 406.48 RIFAPENTINE 877.05LOMIFYLLINE 278.31 LOTEPREDNOL ETABONATE 466.96PAZUFLOXACIN 318.31 ENALAPRILAT 348.40MIGLITOL 207.23 Donepezil 415.96TRANILAST 327.34 Nimetazepam 295.30OLANZAPINE 312.43 NICORANDIL 211.18Nefazodone 506.48 TELMISARTAN 514.63MOXIFLOXACIN HCl 437.90 ITOPRIDE HCl 394.90NELFINAVIR MESYLATE 663.90 RIFAXIMIN 785.89PRAVASTATIN Sodium 446.52 MONTELUKAST Na 608.17TOPOTECAN HCL 457.92 2',3'-DIDEOXYCYTIDINE 211.22LEVETIRACETAM 170.21 1H-Imidazol-2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro 266.56

PRAMIPEXOLE HCl 247.796H-Pyrido[2,3-b][1,4]benzodiazepin-6-one, 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro 421.54

RISPERIDONE 410.49

1H-Indole-2-propanoic acid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-Alpha,Alpha-dimethyl-5-(1-methylethyl) 472.09

PIOGLITAZONE HCl 392.901H-Imidazole-5-carboxylic acid, 1-(1-phenylethyl)-, ethyl ester 244.29

CILASTATIN Na 380.44 Acetamide, 2-amino-N-(1-methyl-1,2-diphenylethyl)-, (+/-) 304.82ARGATROBAN 508.64 Altanserin 474.98VALDECOXIB 314.36 BETAXOLOL HYDROCHLORIDE 343.90NAFTOPIDIL 392.50 INDARUBICIN 262.27Nobiletin 402.40 Azasetron 386.28FINASTERIDE 372.55 GR 89696 530.41

ZOLPIDEM TARTRATE 382.44DELTA1-HYDROCORTISONE 21-HEMISUCCINATE SODIUM SALT 482.51

Viramune 266.30 DIAZOXIDE 230.67TOPIRAMATE 339.36 2-CHLOROADENOSINE 301.69VORICONAZOLE 349.32 ORNIDAZOLE 219.63FENOLDOPAM MESYLATE 401.87 1,1-DIMETHYL-4-PHENYLPIPERAZINIUM IODIDE 318.20ROSIGLITAZONE MALEATE 473.50 PIRENPERONE 393.46ESCITALOPRAM OXALATE 414.43 MESTRANOL 310.44ZERANOL 322.40 2-(2-AMINOETHYL)PYRIDINE 122.17LATANOPROST 432.60 CBENACTYZINE HYDROCHLORIDE 363.892',3'-DIDEOXYINOSINE 236.23 DICHLOROACETIC ACID 128.94Sertraline 342.70 BESTATIN 308.38CALCIPOTRIOL 412.62 TOREMIFENE CITRATE 598.09EPIRUBICIN HYDROCHLORIDE 579.99 GOSERELIN ACETATE 1329.49BICALUTAMIDE 430.37 SECOISOLARICIRESINOL 362.42BENIDIPINE HCl 542.03 RALTITREXED 458.49AMLEXANOX 298.30 DOXAPRAM HYDROCHLORIDE 414.98CERIVASTATIN Na 481.54 RU 24969 287.34ICARIIN 676.67 Brucine 394.47METHYLANDROSTENEDIOL 304.47 TRYPTOLINE 172.23TRIPTOLIDE 360.41 FLUPHENAZINE HYDROCHLORIDE 510.45ROSIGLTAZONE HCl 393.89 PALONOSETRON HCl 332.87FTORAFUR 200.17 NAPROXEN SODIUM 252.25OLIGOMYCIN C 775.08 MEPIVACAINE HYDROCHLORIDE 282.81

BENAZEPRIL HCl 460.963-[3,5-DIBROMO-4-HYDROXYBENZOYL]-2-ETHYLBENZOFURAN 424.09

Oxymetholone 332.49 NIMODIPINE 418.45IPRIFLAVONE 280.32 ROLITETRACYCLINE 527.58

OXAPROZIN 293.32 MEPIRIZOLE 234.26ROLIPRAM 275.35 6-AZAURIDINE 245.19MOSAPRIDE CITRATE 614.02 Reichstein’s substance S 346.47ISOQUERCETRIN 464.38 3-PYRIDINEMETHANOL 109.13FLUMAZENIL 303.29 Haloperidol 412.33OZAGREL HCl 264.71 Stiripentol 234.30HYPEROSIDE 464.38 Fluperlapine 309.39RIFABUTIN 847.02 OXYPHENONIUM BROMIDE 428.41ESMOLOL HYDROCHLORIDE 331.84 Homoveratrylamine 181.24TADALAFIL 389.41 TINIDAZOLE 247.27Modafinil 273.35 XANTHINOL NICOTINATE 434.45DOXORUBICIN HYDROCHLORIDE 579.99 SYNEPHRINE 167.21MOXONIDINE HCl 278.14 RESVERATROL 228.25Nitrazepam 281.27 MALTOL 126.11PEFLOXACIN MESYLATE 429.47 6-AMINOINDAZOLE 133.15VENLAFAXINE HCl 313.87 ENROFLOXACIN 359.40PANTOPRAZOLE SODIUM SALT 405.35 DEHYDROCHOLIC ACID 402.53FLUTICASONE PROPIONATE 500.58 CEFACLOR 367.81INDINAVIR SULPHATE 711.88 1-BENZYLIMIDAZOLE 158.20MIDAZOLAM HCl 362.23 DULOXETINE HCl 333.88LAMIVUDINE 229.25 VARDENAFIL CITRATE 680.73PROCARBAZINE HCl 257.76 ROPIVACAINE HCl 310.87ESOMEPRAZOLE Mg 713.12 ANASTROZOLE 293.37SULFASALAZINE 398.39 KETOTIFEN FUMARATE 425.50TORASEMIDE 348.42 MEDROXYPROGESTERONE 344.50TROPISETRON HCl 320.82 Pinacidil monohydrate 263.34Ranolazine dihydrochloride 500.47 7-NITROINDAZOLE 163.14NITRENDIPINE 360.37 5-Methoxytryptamine 190.25SAQUINAVIR MESYLATE 766.96 PHENOTHIAZINE 199.27BIFONAZOLE 310.40 2-CHLORO-2'-DEOXYADENOSINE 285.69SUMATRIPTAN SUCCINATE 413.49 GRANISETRON HCl 348.88EXEMESTANE 296.41 Rimcazole 403.40NITAZOXANIDE 307.28 Nafadotride 365.48Diazepam 284.75 DESOXIMETASONE 376.47QUETIAPINE HEMIFUMARATE 499.58 DEXCHLORPHENIRAMINE MALEATE 390.87RUTIN 610.53 Guanidine, N-cyano-N'-(1,1-dimethylpropyl)-N''-3-pyridinyl 231.30PENCICLOVIR 253.26 L-694,247 447.51CALCITRIOL 416.65 AM-251 555.25DIPHENOXYLATE 489.06 HTMT 614.57

Felbamate 244.19Benzo[a]phenanthridine-10,11-diol, 5,6,6a,7,8,12b-hexahydro-, trans 335.32

DROPERIDOL 379.44 Methanesulfonamide 474.45

Pentoxifylline 278.312H-Indol-2-one, 1,3-dihydro-1-phenyl-3,3-bis(4-pyridinylmethyl) 468.90

TORADOL 376.41 Beclomethasone 408.92RITONAVIR 720.95 OMEPRAZOLE 345.42VINORELBINE BITATRATE 1079.13 DOLASETRON MESYLATE 420.49LINEZOLIDE 337.35 Zolmitriptan 287.36LOMERIZINE DiHCl 541.47 TREMULACIN 528.51EFAVIRENZ 315.68 DACTINOMYCIN 1255.44IRBESARTAN 428.54 Tramadol 299.84REPAGLINIDE 452.60 CHLORDIAZEPOXIDE 299.76Ethylestrenol 288.48 CEFIXIME TRIHYDRATE 507.49PTEROSTILBENE 256.30 CEFDINIR 395.41ARTEMETHER 298.38 LOFEXIDINE HCl 295.60EBSELEN 274.18 BALSALAZIDE 357.32CGS 12066B 566.49 OLOPATADINE HCl 373.88TELITHROMYCIN 812.02 ITAVASTATIN Ca 881.00CCPA 387.82 CORTISONE 360.45PD 81723 299.31 CYPROHEPTADINE HYDROCHLORIDE 323.87Stanozolol 328.50 HOMOHARRINGTONINE 545.63Zaleplon 305.34 CORTICOSTERONE 346.47Prostaglandin E1 354.49 VECURONIUM BROMIDE 637.75Testosterone 288.43 TIBOLONE 312.45DEHYDROEPIANDROSTERONE 288.43 NICOTINAMIDE 122.13SDM25N 468.98 NIALAMIDE 298.35Thiophene, 5-bromo-2-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl] 411.30 VINDESINE SULFATE 852.025-Nonyloxytryptamine 338.92 VINCRISTINE SULFATE 923.05Salmeterol 415.58 LACIDIPINE 455.55SB 205607 524.30 MIRTAZAPINE 265.36R(+)-SCH-23390 hydrochloride 324.25 AMPIROXICAM 447.46

Allopurinol 136.0 GLIMEPIRIDE 490.62Busulfan 246.3 AMLODIPINE BASE 408.88Thalidomide 258.2 RABEPRAZOLE 359.44Pentostatin 268.3 CLOFAZIMINE 473.41Tamoxifen citrate 563.7 IRINOTECAN HCl (trihydrate) 677.20Rapamycin 914.2 LANSOPRAZOLE 369.36

Estramustine disodium phosphate 566.08-Chloro-11-piperidin-4-ylidene-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine 310.83

Fluorouracil 130.0 1,3,5(10)-ESTRATRIEN-3-OL-17-ONE SULPHATE, SODIUM SALT 372.41Floxuridine 246.2 MIFEPRISTONE 429.60Procarbazine 257.8 Etoposide 588.57Gemcitabine HCl 299.7 Sibutramine 279.85Teniposide 656.7 Clobenpropit 308.83Dactinomycin 1255.4 HUPERZINE A 242.32Acrichine 473.0 SIBUTRAMINE HCl 334.33Hydroxyurea 76.1 Lorazepam 321.16

Methoxsalen 216.0

8-Azaspiro[4.5]decane-7,9-dione, 8-[2-[[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]amino]ethyl]-, monomethanesulfonate 520.26

Streptozocin 265.2 Adenosine, N-(2-hydroxycyclopentyl)-, (1S-trans) 405.84Chlorambucil 304.2 AMIODARONE HYDROCHLORIDE 681.78Irinotecan HCl 623.2 mevastatin 390.52Vinorelbine tartrate 1079.0 IMATINIB MESYLATE 589.72Triethylenemelamine 204.0 Metylperon 299.82Thioguanine 167.0 PARECOXIB Na 392.41Lomustine, CCNU 233.7 PERGOLIDE MESYLATE SALT 410.60Cladribine 286.0 ATRACURIUM BESYLATE 1243.49Mitomycin C 334.3 Methotrexate 454.4Pipobroman 356.1 Oxaliplatin 397.0Aminolevulinic acid 167.6 Thiotepa 189.0Altretamine 210.0 Uracil mustard 252.1Mercaptopurine 152.0 Tretinoin 300.4Carmustine 214.1 Daunorubicin HCl 564.0Ifosfamide 261.1 Topotecan HCl 457.9Mitotane 320.0 Dacarbazine 182.0Megestrol acetate 385.0 Temozolomide 194.2Carboplatin 371.0 Cytarabine HCl 280.0Nitrogen mustard 192.5 Dexrazoxone 268.3Cyclophosphamide 261.0 Etoposide 589.0Cisplatin 300.1 Docetaxel 807.9Pemetrexed 427.4 Arsenic trioxide 198.0Imiquimod 240.3 Fludarabine 365.2Erlotinib HCl 430.0 Bortezomib 384.2Zolendronic acid 272.0 Capecitabine 359.0Amifostine 214.2 Celecoxib 381.0Melphalan 341.7 Sunitinib 398.0Azacitidine 244.2 Mitoxantrone 444.0Decitabine 228.2 Gefitinib 446.9Nelarabine 297.0 Dasatinib 488.0Vorinostat 264.0 Imatinib 493.6Exemestane 296.0 Sorafenib 464.8Anastrozole 293.4 Raloxifene HCl 473.6Letrozole 285.0 Doxorubicin HCl 580.0Lenalidomide 259.3 Lapatinib 581.1Clofarabine 304.0 Fulvestrant 606.8Vinblastine sulfate 909.0 Plicamycin 1085.2Vincristine sulfate 923.0 Valrubicin 723.6Bleomycin 1512.6 Nilotinib 529.5Paclitaxel 853.9 Ixabepilone 506.7Everolimus 958.0

Supplementary Table 2

NF90.8 cell line

Compounds Target(s) Drug (µM)/R2 Drug + rapamycin (25% of IC50) (µM)/R2

Drug + everolimus (25% of IC50) (µM)/R2

Saquinavir protease inhibitor 46.6/0.99 45.2/0.97 48.4/0.99Ifenprodil N-methyl-d-aspartate (NMDA) receptors 198.3/0.98 267.7/0.98 187.6/0.96Rosiglitazone PPAR gamma agonist 576.2/0.84 1150/0.94 684.5/0.89Dichloroacetate pyruvate dehydrogenase kinase >1000 ND NDToremifene estrogen receptor modulator 34.6/0.99 19.0/0.97 20.1/0.99Riluzole glutamate release inhibitor 91.4/0.99 72.7/0.94 72.7/0.96Lapatinib EGFR and ERBB2 9.6/0.98 16.0/0.97 12.8/0.98Vandetanib EGFR, RET, VEGFR 59.4/0.97 60.5/0.94 62.8/0.96Pazopanib VEGFR, PDGF, c-KIT 20.1/0.97 44.4/0.93 37.3/0.93Bortezomib proteasome 0.080/0.99 0.032/0.99 0.057/0.99

T265-2C cell line

Compounds Target(s) Drug (µM)/R2 Drug + rapamycin (25% of IC50) (µM)/R2

Drug + everolimus (25% of IC50) (µM)/R2

Toremifene estrogen receptor modulator 22.6/0.99 18.1/0.99 21.0/0.99Riluzole glutamate release inhibitor 106.5/0.96 80.9/0.96 119.3/0.95Bortezomib proteasome 0.053/0.98 0.033/0.99 0.037/0.99

sNF96.2 cell line

Compounds Target(s) Drug (µM)/R2 Drug + rapamycin (25% of IC50) (µM)/R2

Drug + everolimus (25% of IC50) (µM)/R2

Toremifene estrogen receptor modulator 22.1/0.99 12.9/0.97 11.2/0.99Riluzole glutamate release inhibitor 97.3/0.84 94.5/0.97 97.9/0.97Bortezomib proteasome 0.095/0.97 0.045/0.98 0.079/0.98

Cell line Compounds Drug (µM)/R2 Drug + bortezomib (25% of IC50) (µM)/R2

NF90.8rapamycin 27.2/0.98 18.0/0.99everolimus 30.0/0.99 16.9/0.99

T265-2Crapamycin 19.2/0.99 13.6/0.98everolimus 15.6/0.99 10.7/0.98

sNF96.2rapamycin 48.9/0.98 15.0/0.97everolimus 28.2/0.98 14.5/0.96

Supplementary Table 3

Supplementary Table 4NF90.8

T265-2C

sNF96.2

rapa (µM)

eve (µM) borte (nM) FA CI rapa

(µM)eve (µM) borte (nM) FA CI rapa

(µM)eve (µM) borte (nM) FA CI

12.5 0.1 0.20 1.43 10.5 0.1 0.42 1.21 13 0.1 0.15 2.7212.5 1 0.23 1.27 10.5 1 0.42 1.25 13 1 0.15 2.9112.5 10 0.28 1.22 10.5 10 0.45 1.34 13 10 0.23 1.3512.5 100 0.82 0.17 10.5 100 0.91 0.05 13 100 0.67 0.0825 0.1 0.45 1.09 21 0.1 0.64 0.87 27 0.1 0.32 1.3625 1 0.49 0.96 21 1 0.67 0.75 27 1 0.33 1.2925 10 0.69 0.49 21 10 0.84 0.24 27 10 0.64 0.2025 100 0.88 0.20 21 100 0.99 6.0E-06 27 100 0.90 0.0137 0.1 0.59 1.03 31 0.1 0.71 0.89 40 0.1 0.47 0.8037 1 0.63 0.90 31 1 0.77 0.61 40 1 0.54 0.5437 10 0.89 0.25 31 10 0.94 0.09 40 10 0.98 2.0E-0337 100 0.99 0.03 31 100 0.99 5.1E-05 40 100 0.99 1.1E-06

5 0.1 0.21 0.93 4.8 0.1 0.26 1.34 5.9 0.1 0.07 4.245 1 0.20 1.05 4.8 1 0.32 0.97 5.9 1 0.12 1.905 10 0.22 1.25 4.8 10 0.29 2.47 5.9 10 0.14 1.825 100 0.88 0.03 4.8 100 0.82 0.05 5.9 100 0.58 0.07

10 0.1 0.13 3.78 9.6 0.1 0.49 0.53 11.8 0.1 0.15 2.7110 1 0.20 2.05 9.6 1 0.55 0.36 11.8 1 0.21 1.4610 10 0.26 1.59 9.6 10 0.45 0.91 11.8 10 0.29 0.8510 100 0.89 0.04 9.6 100 0.93 8.0E-03 11.8 100 0.72 0.0615 0.1 0.45 0.71 14 0.1 0.46 0.98 17 0.1 0.32 1.0315 1 0.41 0.87 14 1 0.48 0.85 17 1 0.33 0.9115 10 0.59 0.38 14 10 0.59 0.47 17 10 0.49 0.37

15 100 0.95 0.01 14 100 0.97 1.0E-03 17 100 0.85 0.02