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ALK4L75A-Fc
- Development stage
- Preclinical
- Lead developer
- Salk Institute for Biological Studies
- Modality
- Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes
- Administration
- Parenteral, Intravenous, Subcutaneous, Intramuscular, Intradermal, Intrathecal, Intra-arterial, Intraperitoneal, Intratumoral, Intralesional, Intravesical, Intravitreal, Intraarticular, Oral, Topical, Inhalation, Intranasal, Rectal, Vaginal, Transdermal, Implant
01
Overview
ALK4L75A-Fc (also known as A4Fc) is a recombinant fusion protein designed as a selective antagonist of CRIPTO (Cripto-1 / TDGF1). It consists of a human IgG Fc domain fused to a mutant extracellular domain of activin-like kinase 4 (ALK4), a natural type I receptor partner of CRIPTO. The ALK4 domain contains a specific point mutation (L75A) that disrupts its binding to TGF-beta superfamily ligands (such as activin and Nodal) while preserving its high-affinity interaction with CRIPTO. By sequestering CRIPTO, ALK4L75A-Fc inhibits CRIPTO-dependent signaling pathways, including those mediated by cell-surface GRP78. This blockade suppresses cancer cell plasticity, epithelial-mesenchymal transition (EMT), and the maintenance of cancer stem cell phenotypes, particularly under microenvironmental stresses like nutrient deprivation, hypoxia, and chemotherapy. Developed by researchers at the Salk Institute and the University of Utah, ALK4L75A-Fc is being investigated preclinically for the treatment of triple-negative breast cancer and the prevention of metastasis.
- Other names
- A4FcA-4FcA 4FcALK4(L75A)-Fc
02
Targets
TDGF1 (Teratocarcinoma-derived growth factor 1)ACVR1B (Activin A receptor type IB)
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