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metformin + tegafur + gimeracil + oteracil
- Development stage
- Unknown
- Lead developer
- Agency for Medical Research and Development
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
MIKE-1 is an oral combination regimen consisting of the biguanide metformin and the multi-component fluoropyrimidine S-1 (a combination of tegafur, gimeracil, and oteracil). Developed for the treatment of unresectable pancreatic adenocarcinoma, MIKE-1 is typically evaluated in combination with standard chemotherapy agents like gemcitabine and nab-paclitaxel. The rationale behind the combination is that metformin may enhance the efficacy of chemotherapy by activating AMP-activated protein kinase (AMPK) and inhibiting the mTOR pathway, which are often dysregulated in pancreatic cancer cells. S-1 provides a sustained release of 5-fluorouracil (5-FU) while incorporating gimeracil to inhibit its degradation and oteracil to reduce gastrointestinal toxicity. This combination aims to improve survival outcomes in patients with previously untreated, advanced pancreatic cancer.
- Other names
- Metformin + S-1Metformin/S-1
02
Targets
AMPK (Adenosine monophosphate–activated protein kinase)ND1 (Mitochondrial electron transport chain complex I)DPYD (Dihydropyrimidine dehydrogenase)TS (Thymidylate synthase)Mechanistic target of rapamycin complex 1DNAOPRT (Orotidine 5'-phosphate decarboxylase)
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