Programs
Caldan Therapeutics initial focus is on activators of free fatty acid receptors implicated in metabolic diseases such as Type 2 Diabetes and non-alcoholic steatohepatitis (NASH) drawing on its experience of GPCR targets.
Caldan is focused on Research and Development programmes that would be expected to address multiple aspects of T2D pathophysiology including insulin secretion, insulin sensitivity, islet cell protection, anti-inflammatory activity in muscle, liver and adipose tissue, weight loss, and decreased hepatic steatosis. This would be a step change in the treatment of T2D as it has the potential to deliver oral small molecules with the potential for glucose-lowering agents at least as good as currently marketed compounds but with additional benefits.
Caldan has exclusive commercial access to proprietary sensors developed at UoG, which will provide a considerable competitive edge in characterising the compounds and tailoring them to the ideal profile.
Key publications from Milligan/Ulven labs
Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity. Carlos M. G. Azevedo, Kenneth R. Watterson, Ed T Wargent, Steffen V. F. Hansen, Brian D. Hudson, Małgorzata A. Kępczyńska, Julia Dunlop, Bharat Shimpukade, Elisabeth Christiansen, Graeme Milligan, Claire J Stocker, and Trond Ulven – J. Med.Chem. 2016 Oct 13;59(19):8868-8878.
Complex Pharmacology of Free Fatty Acid Receptors. Milligan G, Shimpukade B, Ulven T, Hudson BD
Chem. Rev. 2017 Jan 11;117(1):67-110.
Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4. Milligan G., Alvarez-Curto E, Watterson KR, Ulven T, Hudson BD. Br J Pharmacol. 2015 Jul;172(13):3254-65.
The molecular basis of ligand interaction at free fatty acid receptor 4 (FFA4/GPR120). Hudson BD, Shimpukade B, Milligan G, Ulven T. J Biol Chem. 2014 Jul 18;289(29):20345-58.
The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism. Hudson BD, Shimpukade B, Mackenzie AE, Butcher AJ, Pediani JD, Christiansen E, Heathcote H, Tobin AB, Ulven T, Milligan G. Mol Pharmacol. 2013 Nov;84(5):710-25.
Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. Christiansen E, Due-Hansen ME, Urban C, Grundmann M, Schmidt J, Hansen SV, Hudson BD, Zaibi M, Markussen SB, Hagesaether E, Milligan G, Cawthorne MA, Kostenis E, Kassack MU, Ulven T. J Med Chem. 2013 Feb 14;56(3):982-92.
Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes. Christiansen E, Hansen SV, Urban C, Hudson BD, Wargent ET, Grundmann M, Jenkins L, Zaibi M, Stocker CJ, Ullrich S, Kostenis E, Kassack MU, Milligan G, Cawthorne MA, Ulven T. ACS Med Chem Lett. 2013 May 9;4(5):441-445.
Discovery of a potent and selective GPR120 agonist. Shimpukade B, Hudson BD, Hovgaard CK, Milligan G, Ulven T. J Med Chem. 2012 May 10;55(9):4511-5.
