Interrogating the Inner Life of GPCR Signaling to Develop New Therapeutics
Our discovery team has significant expertise in understanding and creating product candidates to influence the dynamic behavior of G-protein coupled receptors (GPCRs) and has developed a number of proprietary methods, techniques and tools that we believe will enable us to efficiently and reliably evaluate newly synthesized molecules. We employ an iterative strategy where compounds are designed, synthesized and rapidly characterized for pharmacologic and pharmaceutical properties.
There are more than 80 known peptide hormones acting at more than 120 known different receptors. Historically, it was assumed that small molecules could not replicate or compete with the complex interactions between peptides and their cognate GPCRs. As such, most drugs developed for peptide GPCRs have been and continue to be peptides themselves, which present manufacturing and formulation difficulties and force patients to undergo frequent injections because peptides generally are not orally bioavailable.
With each of our drug discovery programs, our goal is to specifically tailor a product candidate with pharmacologic and pharmaceutical properties highly optimized for its interaction with its specific GPCR target that we anticipate will translate to downstream benefits in our chosen therapeutic applications.
Selective Somatostatin Subtype 5 (sst5) Agonists for the Treatment of Hyperinsulinism: Orally-Bioavailable Small Molecules Suppress Insulin and Rescue Glyburide-Induced Hypoglycemia.
Markison S, Kusnetzow AK, Shin R, Sturchler E, Zhao J, Zhu YF, Struthers RS, Betz SF. ENDO 2018. March 17-20, 2018; Chicago.
Suppression of Growth Hormone and Insulin-Like Growth Factor 1 in Rats After Oral Administration of CRN00808, a Small Molecule, sst2 Selective Somatostatin Biased Agonist.
Betz SF, Markison S, Kusnetzow AK, Athanacio JD, Rico-Bautista E, Madan A, Johns M, Zhu YF, Schonbrunn A, Struthers RS. ENDO 2018. March 17-20, 2018; Chicago.