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selinexor + orelabrutinib + methotrexate
- Development stage
- Unknown
- Lead developer
- The Second Affiliated Hospital of Dalian Medical University
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination regimen consists of the XPO1 inhibitor selinexor, the Bruton's tyrosine kinase (BTK) inhibitor orelabrutinib, and high-dose methotrexate (HDMTX). It is being investigated as a treatment for primary and secondary central nervous system lymphoma (CNSL). Selinexor works by inhibiting Exportin 1 (XPO1), leading to the nuclear retention and activation of tumor suppressor proteins. Orelabrutinib is a highly selective, irreversible BTK inhibitor that disrupts B-cell receptor signaling, which is critical for the survival of malignant B-cells. Methotrexate is an antimetabolite that interferes with DNA synthesis. The combination aims to leverage the synergistic effects of targeted therapy and traditional chemotherapy to penetrate the blood-brain barrier and improve outcomes in aggressive B-cell lymphomas involving the central nervous system.
- Other names
- XPO1 inhibitor + BTK inhibitor + methotrexateSelinexor + Orelabrutinib + HDMTX
02
Targets
DHFR (Dihydrofolate reductase)BTK (Bruton tyrosine kinase)XPO1 (Exportin-1)
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