S5: Elevated cytoplasmic ROS induces apoptosis after the treatment with neocuproine

Table ST2: Summary of the clinical data corresponding to the primary cell cultures used in this publication

Table ST5: Table of the 15 most informative proteins upregulated in MEK inhibitor-resistant cell culture (ranked by log2 fold-change).

Table ST6: Differential expressed lipids and their FDRs in sensitive vs resistant cells (negative values are upregulated in sensitive cells).

S3: Correlation between MEKi responsiveness and sensitivity to nNeocuproine

Table ST3: Differential expressed RNA transcripts between MEKi-sensitive and -resistant melanoma cell cultures.

Table ST1: Summary of growth inhibitory IC50 values (including the corresponding 95% confident intervals (C.I.95%) conducted for neocuproine or MEKi (binimetinib) and primary human cell lines. The table includes the confirmed oncogenic mutation as well as the ratio of neocuproine normalized to the MEKi response.

S2: HPLC analysis of STO13881 and nNeocuproine showed overlapping profiles and confirmed STO13881 to be neocuproine (purchased from Sigma-Aldrich, Switzerland). High-performance liquid chromatography (HPLC) analysis was performed using the Zuürich functional genomic center.

S7: Pathway enrichment (metabolomics)

S9: Treatment of binimetinib-sensitive melanoma cell lines with PPP inhibitor

S11: Immunohistological analysis of orthologic slice cultures.

Table ST4: Table of the 15 most informative proteins upregulated in MEK inhibitor-sensitive cell culture (ranked by log2 fold-change).

Table ST7: Clinical data of the 62 melanoma patient which tumor material was used for pharmacoscopy

S12: Analysis of CyTof data from fresh melanoma tissue

S16: scRNA-sequencing analysis of xenograft tumors M130227

Tumor Profiler Consortium author list

Table ST8: Data output of the CCLE cell line screening provided by Prof. Schreiber at Broad Institute.

S4: Neocuproine is a copper-dependent ROS inducer