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Published byChristopher Ross Modified over 9 years ago
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Compound 5 Structure hLDHA IC 50 0.032 ± 0.016 µM hLDHB IC 50 2.512 ± 0.07 µM Supplementary Figure S1
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Supplementary Figure S2 Compound 2 -9-8-7-6-5 % inhibition 25 50 75 100 5 M 30 M 60 M 120 M B A concentration in cell, M Cmpd 1Cmpd 2Cmpd 3 NADHCmpd IC50 67 nM 43 nM 22 nM 12 nM
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13 C 15 N- Arg/Lys HEK293 SILAC Mix 1:1 Ratio SNU398 12 C 14 N- Arg/Lys Protein Concentration Prepare lysates triplicate Protein Concentration recomb LDHA Spike 13 C 15 N- Arg/Lys HEK293 SILAC Supplementary Figure S3 Trypsin digest LC-MS/MS Trypsin digest LC-MS/MS B A Snu398 HepG2 LDHA copies/cell LDHA cell concentration 4.7 x 10 6 2.9 x 10 6 2.6 1.5 C Hek293 3.8 x 10 6 5.4 MM 973 975 977 Relative Intensity % 0 100 rLDHA HEK293 Relative Intensity % 0 100 973 975 977 HEK293Snu398 LLIVSNPVDILTYVAWK
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LDHA LDHB A CD Snu398MDA-MB-453MiaPaCa-2NCI-H1395Snu423U251A2780Cal-27HepG2786-O LDHA, M -actin Supplementary Figure S4 7=042 LDHA 234 trxn 2, days trxn 1, days WB + + + + + + + LDHAsi 7 E HepG2KidneyMelanomaLiverColonPancreasBreast LDHA -actin LDHB LDHA, M B
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Supplementary Figure S5
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FBP, nmol/mln cells DMSOCmpd 1Cmpd 2 Supplementary Figure S6 FBP, nmol/mln cells < 0.3 DMSOCmpd 1Cmpd 2 A B
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Supplementary Figure S7
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relative pathway activity HepG2Snu398 pentose phosphate glycolysis fatty acid synthesis glutaminolysis Supplementary Figure S8 A B
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