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Target intelligence / Profile preview
Glial cell line-derived neurotrophic factor family receptor alpha-like (GFRAL)
- Target
- GFRAL
- Molecular classification
- Receptor, GDNF receptor family
01
Overview
GFRAL is the primary high-affinity receptor for GDF15, a cytokine involved in appetite suppression and energy homeostasis. GFRAL is expressed predominantly in the area postrema and nucleus tractus solitarius of the brainstem. Upon binding GDF15, GFRAL forms a complex with the co-receptor RET, activating downstream signaling pathways. Targeting the GDF15/GFRAL interaction is being explored as a therapeutic strategy for obesity and cancer-related cachexia. Some effects of GDF15 may be mediated independently of GFRAL or through other receptors such as TGF-beta type II/type I receptors or EGFR2.
- Other names
- GDNF family receptor alpha-likeGDNF receptor alpha-likeGFRAL receptor
02
Mechanism of action
Currently, under research, small molecules or antibodies that can block the GDF15/GFRAL axis for therapeutic benefit by mimicking/suppressing this pathway to modulate appetite or inhibiting excessive pathway activation seen in chronic disease states like cancer.
03
Biological functions
Signal transductionAppetite suppressionEnergy homeostasisBody weight regulation
04
Disease associations
ObesityMetabolic disordersCancerCachexiaInflammation
05
Safety considerations
Potential for off-target effects due to similarity to TGF-beta receptorsRisk of disrupting normal appetite regulationPossible CNS-related side effects due to restricted expression in the brainstem
06
Biomarkers
GDF15 levels as a predictive marker for cachexiaGFRAL expression levels in brainstem as a measure of target engagement
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