Careers & Students

AMPK allosteric inhibitors

AMPK allosteric inhibitors

PhD project

A range of nutrient, hormonal, and cytokine signals contribute to energy homeostasis through inhibition of the master metabolic regulator AMP-activated protein kinase (AMPK). Pharmacological inhibition of AMPK is beneficial in a range of disease settings, e.g. diabetes (augmentation of glucose-stimulated insulin secretion), cancer (suppression of tumor growth), stroke (neuroprotection), obesity (appetite regulation) and Alzheimer’s disease. The canonical AMPK inhibitor compound C competes with ATP at the kinase active site but is non-selective. We have characterized MT47-100, the first reported small compound AMPK inhibitor that acts through the CBM allosteric drug site. This finding represents a major milestone in the development of this much understudied area of drug design. Projects are available aimed at developing more potent AMPK allosteric inhibitors and evaluating the effectiveness of therapeutic AMPK inhibition in a diverse range of applications.

Training will be provided in a number of techniques including molecular biology, protein biochemistry, protein expression and purification, crystallography, mass spectrometry, primary cell culture, genetic mouse models.

Collaborators:  Dr Kristy Brown, Hudson Institute of Medical Research; Prof Jonathan Baell, Monash Institute of Pharmaceutical Sciences.

Supervised by:

  • Associate Professor Jonathan Oakhill
  • Dr John W. Scott
  • Prof Bruce E. Kemp
  • Dr Sandra Galic
  • Dr Christopher Langendorf
  • Disease Focus:

  • Type 2 diabetes
  • Research Unit:

  • Metabolic signalling