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Antidiabetic activity of MTP-3115 in normal and diabetic mice
T T Yen1, N B Dininger, C L Broderick
1Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Abstract:
MTP-3115 is a newly-synthesized thiopyranopyrimidine compound with a structure similar to that of MTP-1403 and MTP-1307. However, the biological profile of MTP-3115 is different from that of MTP-1403 and MTP-1307 (previously reported). Similar to MTP-1403 and MTP-1307, MTP-3115 improves glucose tolerance in both normal and obese-diabetic viable yellow mice with equal potency. However, unlike MTP-1403 and MTP-1307, MTP-3115 also lowers blood glucose of fed and fasted normal and obese-diabetic viable yellow mice. Although the mechanisms of action of MTP-3115 are not elucidated, it is unlikely that its mode of action is similar to that of sulfonylureas because tolbutamide neither improves glucose tolerance nor lowers blood glucose in obese-diabetic viable yellow mice.
Insights
A new compound, MTP-3115, improves glucose tolerance and lowers blood glucose in mice. Unlike related compounds, MTP-3115 demonstrates a broader glucose-lowering effect, suggesting a novel mechanism of action.
Area of Science:
- Pharmacology
- Endocrinology
- Medicinal Chemistry
Background:
- MTP-3115 is a novel thiopyranopyrimidine compound.
- Its structural similarity to MTP-1403 and MTP-1307 suggests potential shared biological activities.
- However, preliminary data indicate distinct pharmacological profiles.
Purpose of the Study:
- To investigate the glucose-modulating effects of MTP-3115 in viable yellow mice.
- To compare the efficacy of MTP-3115 with related compounds (MTP-1403, MTP-1307) and sulfonylureas.
- To explore potential mechanisms of action for MTP-3115.
Main Methods:
- Administration of MTP-3115 to normal and obese-diabetic viable yellow mice.
- Assessment of glucose tolerance and blood glucose levels in fed and fasted states.
- Comparative analysis with MTP-1403, MTP-1307, and tolbutamide.
Main Results:
- MTP-3115 demonstrated equal potency to MTP-1403 and MTP-1307 in improving glucose tolerance.
- Unlike MTP-1403 and MTP-1307, MTP-3115 significantly lowered blood glucose in both normal and obese-diabetic mice under fed and fasted conditions.
- Tolbutamide, a sulfonylurea, showed no effect on glucose tolerance or blood glucose levels in obese-diabetic mice, suggesting MTP-3115's mechanism differs.
Conclusions:
- MTP-3115 exhibits potent glucose-lowering properties in viable yellow mice.
- Its distinct pharmacological profile, particularly its ability to reduce blood glucose, differentiates it from structurally similar compounds.
- The mechanism of action of MTP-3115 is likely distinct from sulfonylureas.
