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cisplatin + pemetrexed + regorafenib
- Development stage
- Unknown
- Lead developer
- Bayer
- Modality
- Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules, Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Reversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules, Allosteric Modulators → Classical Binding Small Molecules → Small Molecules, Irreversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules, Fragment-Derived Small Molecules → Multivalent & Scaffold-Based Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
- Administration
- Intravenous, Oral
01
Overview
This is a combination regimen consisting of three drugs: - **Cisplatin** is a platinum-based chemotherapy agent that causes DNA crosslinking and damage, leading to apoptosis in rapidly dividing cells. - **Pemetrexed** is an antifolate antineoplastic agent that inhibits several folate-dependent enzymes involved in the synthesis of nucleotides, thereby disrupting DNA and RNA synthesis. - **Regorafenib** is an oral small-molecule multikinase inhibitor with potent antiangiogenic activity. It targets multiple protein kinases involved in tumor angiogenesis (such as VEGFR), oncogenesis (including KIT, RET, RAF), and the tumor microenvironment. The combination has been studied primarily for advanced nonsquamous non-small cell lung cancer (NSCLC). Early-phase clinical trials indicate acceptable tolerability and minor pharmacokinetic interactions among these agents. The regimen aims to combine cytotoxic effects from cisplatin/pemetrexed with targeted antiangiogenic and antiproliferative effects from regorafenib. Mechanistically, regorafenib can inhibit EGFR/NF-ĸB signaling pathways activated by cisplatin, enhance cytotoxicity, reduce metastatic potential by lowering VEGF/MMP expression, and provide additional antitumor activity beyond standard chemotherapy[1][2][3][4].
- Brand names
- StivargaPlatinolAlimta
- Other names
- regorafenib + cisplatin + pemetrexed
02
Targets
GART (GAR transformylase)ATIC (Aminoimidazole carboxamide ribonucleotide transformylase)DHFR (Dihydrofolate reductase)TS (Thymidylate synthase)
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