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Target intelligence / Profile preview
Smad family member 7 (SMAD7)
- Target
- SMAD7
- Molecular classification
- Transcription factor, Intracellular signaling modulator, TGF-β signaling pathway inhibitor
01
Overview
Smad family member 7 (SMAD7) is a protein encoded by the human SMAD7 gene located on chromosome 18. It serves as a direct intracellular antagonist of TGF-β and BMP receptor signaling by binding to the activated type I receptors and preventing phosphorylation of receptor-regulated Smads, thereby inhibiting downstream signal transduction. SMAD7 also recruits E3 ubiquitin ligases (such as SMURF1, SMURF2, and NEDD4L) to direct receptor degradation—a key negative feedback mechanism. Aberrant SMAD7 function or expression is associated with pathological states like cancer, chronic inflammation, and tissue fibrosis, reinforcing its relevance as a therapeutic target and biomarker for disease prognosis and response.
- Other names
- SMAD7MAD homolog 7Mothers against decapentaplegic homolog 7
02
Mechanism of action
Antisense oligonucleotides downregulate SMAD7 to restore TGF-β signaling. Small molecules can inhibit or stabilize SMAD7 interactions, modulating downstream effects
03
Biological functions
Negative regulation of TGF-β signalingSignal transductionCell proliferation regulationApoptosis inhibitionImmune response modulation
04
Disease associations
Cancer (often mutated or dysregulated in tumors)FibrosisInflammationAutoimmune diseases
05
Safety considerations
Over-inhibition may result in excessive TGF-β signaling, contributing to tissue fibrosis or tumor progression.Suppression can impact immune function and tissue homeostasis
06
Interacting drugs
No approved direct SMAD7-targeting drugs; but antisense oligonucleotides and small molecules targeting SMAD7 are under investigation for inflammatory bowel disease, cancer, and fibrotic conditions (e.g., Mongersen)
07
Biomarkers
Elevated or reduced SMAD7 expression levels (for disease diagnostics in cancer, inflammatory bowel disease, fibrosis)
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