Western life style has spurred the growth of numerous obesity related disorders including metabolic syndrome, type 2 diabetes and certain types of cancers to epidemic proportions. Maintaining cellular energy is a basic biological need mediated in part through amp-activated protein kinase (AMPK), therefore controlling cellular energy metabolism can play a role in treating metabolism related disorders. Indeed, AMPK regulation has been a proposed target of pharmaceutical companies, with no major clinical successes yet. Our proposal seeks to identify novel small molecules that interact with the regulatory fragment of AMPK, rather than the traditional approach of targeting the AMPK kinase domain. Currently available chemical probes/tool compounds for AMPK lack the selectivity for AMPK and hit numerous other kinases due to conserved ATP-binding kinase domains throughout the kinome. Our approach has the potential to deliver selective AMPK regulation through the non-canonical regulatory domain that can have clinical translational potential in the treatment of human diseases.

Public Health Relevance

This proposal seeks to develop new drug-like small molecules to modulate AMP- activated protein kinase (AMPK) activity. AMPK is a central molecular regulator of energy homeostasis with proposed therapeutic potential to treat metabolic diseases including type 2 diabetes, metabolic syndrome, fatty liver disease, and cancer. Therefore this grant will allow generation of potential new therapeutics for these diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43DK101229-01A1
Application #
8781765
Study Section
Special Emphasis Panel (ZRG1-EMNR-S (10))
Program Officer
Arreaza-Rubin, Guillermo
Project Start
2014-09-10
Project End
2015-08-31
Budget Start
2014-09-10
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$297,399
Indirect Cost
Name
Curl Bio, LLC
Department
Type
DUNS #
078505181
City
Durham
State
NC
Country
United States
Zip Code
27707