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Drug intelligence / Profile preview
afatinib + selumetinib
- Development stage
- Phase 2
- Lead developer
- Boehringer Ingelheim
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Afatinib + selumetinib is a combination therapy that targets both the EGFR and MEK pathways. Afatinib is a pan-HER inhibitor that covalently binds to and irreversibly blocks signaling from all homo and heterodimers formed by the ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4. Selumetinib is a selective MEK1/2 inhibitor that blocks the RAS-RAF-MEK-ERK signaling cascade. The combination was developed to overcome resistance mechanisms in KRAS-mutated tumors, where MEK inhibitors alone have limited efficacy due to feedback activation of upstream epidermal growth factor receptors. This upstream activation not only reactivates MAPK but also the phosphoinositide 3-kinase (PI3K)-AKT pathway.
02
Targets
EGFR (Epidermal growth factor receptor)ERBB2 (Erb-b2 receptor tyrosine kinase 2)ERBB4 (Erb-b2 receptor tyrosine kinase 4)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)
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