Compound C/Dorsomorphin: Its Use and Misuse as an AMPK Inhibitor

Area of Science:

• Biochemistry
• Molecular Biology
• Physiology

Background:

• AMP-activated protein kinase (AMPK) is an evolutionarily conserved energy sensor.
• AMPK is critical for embryonic development, adult stress physiology, and metabolic diseases like diabetes and cancer.
• Specific inhibitors for AMPK are lacking, unlike for other medically relevant kinases.

Purpose of the Study:

• To discuss the utility and limitations of using non-specific kinase inhibitors to study AMPK.
• To evaluate the pros and cons of dorsomorphin (compound C) as an AMPK inhibitor.

Main Methods:

• Review of existing literature on AMPK function and inhibitor specificities.
• Analysis of the inhibitory profiles of dorsomorphin (compound C) against AMPK and other kinases.

Main Results:

• Dorsomorphin (compound C) is frequently used as an AMPK inhibitor but exhibits significant off-target kinase inhibition.
• The non-specific nature of dorsomorphin (compound C) complicates the interpretation of experimental results attributed to AMPK inhibition.

Conclusions:

• The lack of specific AMPK inhibitors poses a significant challenge for studying its diverse biological roles.
• Researchers must carefully consider the non-specific effects of dorsomorphin (compound C) when designing experiments and interpreting data related to AMPK.