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Dalantercept + sorafenib
- Development stage
- Discontinued
- Lead developer
- Merck
- Modality
- Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Dalantercept + sorafenib is an investigational combination therapy for advanced cancers, particularly hepatocellular carcinoma (HCC). Dalantercept is a soluble activin receptor-like kinase 1 (ALK1) receptor fusion protein that acts as a ligand trap for bone morphogenetic proteins 9 and 10 (BMP9/10), thereby inhibiting ALK1 signaling and disrupting the maturation of blood vessels through a mechanism distinct from the VEGF pathway. Sorafenib is an oral multikinase inhibitor that targets several kinases including VEGF receptors, PDGF receptors, RAF kinases, and others to inhibit tumor cell proliferation and angiogenesis. The rationale for combining these agents is to achieve enhanced inhibition of tumor angiogenesis by blocking both early (VEGF-mediated) and late (ALK1-mediated) stages of blood vessel formation. This combination has been studied in phase Ib clinical trials in patients with advanced HCC[1][3][6].
- Brand names
- Nexavar
02
Targets
BMP10 (Bone morphogenetic protein 10)BMP9 (Bone morphogenetic protein 9)BRAF (B-Raf proto-oncogene, serine/threonine kinase)FGFR1 (Fibroblast growth factor receptor 1)FLT3 (Fms related receptor tyrosine kinase 3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFRB (Platelet-derived growth factor receptor beta)RET (Rearranged during transfection receptor tyrosine kinase)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)ACVRL1 (Activin receptor-like kinase 1)RAF1 (c-Raf-1 (Y340D/Y341D))
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