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Direct Targeting of the Oncogene Microphthalmia-Associated Transcription Factor (MITF) by Fragment-Based Discovery [RNA-seq]

GSE283855 Homo sapiens (human) RNA-seq (gene expression) 42 samples Submitted 2025/11/26 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 42 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
42 samples: 14 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Fragment-based discovery enables direct targeting of the melanoma oncogene MITFNature communications · 2025
Summary (written by the submitters)
Despite the improvement of therapeutic options for melanoma, patients with advanced metastatic disease are still in high need of durable and tolerated treatments. Analysis of clinical data from patients receiving targeted and/or immunotherapy, along with genetic and functional studies in preclinical melanoma models, show that lineage addiction to MITF is retained throughout disease progression, thus providing the rationale to pursue therapeutic inhibition of MITF.
Read the full summary ↓
However, direct targeting of MITF or other basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors is unprecedented. Here, we report on the fragment-based discovery of high-affinity ligands for MITF. Fragment screening by NMR led to the discovery of weak binders to the kink pocket of MITF, which were optimized to sub-micromolar affinity by structure-based design enabled by crystallography and biophysics. Furthermore, NMR experiments and molecular dynamics simulations revealed a dynamic conformational exchange of the two helices in the asymmetric homodimer, which is perturbed by ligand binding. This work advances our knowledge on direct targeting of bHLH-LZ domains and sets the basis to further explore pharmacological inhibition of MITF.
Published in
Fragment-based discovery enables direct targeting of the melanoma oncogene MITF
Castelletti D, Hinrichs J, Malojčić G et al. · Nature communications 2025 · PMID 41365902 · doi:10.1038/s41467-025-67297-0
This dataset
Open GSE283855 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE283855_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1195918 and SRA study SRP550254. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41365902) ↗
Study design
14 conditions, mostly in triplicate
MELHO_Resistant_MITF_KD ×3 MELHO_Resistant_ctrl ×3 MELHO_Sensitive_MITF_KD ×3 MELHO_Sensitive_ctrl ×3 UACC257_A264C_DOX ×3 UACC257_A264C_NoDOX ×3 UACC257_K243A_DOX ×3 UACC257_K243A_NoDOX ×3 +6 more

Supports a between-group comparison across 42 samples.

How we read this: 14 replicated groups read from 42 sample titles; they account for 42 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 2 more — browse all 42 samples with per-sample file links →

Datasets on a similar topic

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