crinetics approach

Our Approach

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.

Scientific Presentations

2019

Nonpeptide, Orally Bioavailable ACTH Antagonists: Suppression of ACTH-induced
Corticosterone Secretion and Adrenal Hypertrophy in Rats

Ana Karin Kusnetzow, Melissa A. Fowler, Jon Athanacio, Greg Reinhart, Elizabeth Rico-Bautista, Sangdon Han, Sun Hee Kim, Michael Johns, Taylor A. Kredel, Julie Nguyen, Christine Staley, Hannah Tan, Rosa Luo, Stacy Markison, Ajay Madan, Yun Fei Zhu, R. Scott Struthers, and Stephen F. Betz. ENDO 2019. March 23-26, 2019; New Orleans.

Selective Nonpeptide Somatostatin Receptor Subtype 5 (sst5) Agonists Suppress Glucose- and Sulfonylurea-induced Insulin Secretion in Rats
Emmanuel Sturchler, Melissa A. Fowler, Jon Athanacio, Taylor A. Kredel, Michael Johns, Jian Zhao, Shimiao Wang, Rosa Luo, Ana Karin Kusnetzow, Yun Fei Zhu, Ajay Madan, R. Scott Struthers, Stephen F. Betz, Stacy Markison. ENDO 2019. March 23-26, 2019; New Orleans.

Selective Nonpeptide Somatostatin Subtype 5 (sst5) Agonists Suppress Induced Insulin
Secretion in Pancreatic Islets from both Rats and Healthy Human Donors.

Elizabeth Rico-Bautista, Ana Karin Kusnetzow, Melissa A. Fowler, Jon Athanacio, Taylor A. Kredel, Jian Zhao, Shimiao Wang, Stacy Markison, Yun Fei Zhu, R. Scott Struthers, Stephen F. Betz. ENDO 2019. March 23-26, 2019; New Orleans.

Final Results from the First in Man Phase 1 Clinical Trial of CRN00808, an Orally Bioavailable sst2-Selective, Nonpeptide Somatostatin Biased Agonist for the Treatment of Acromegaly: Safety, Pharmacokinetics, Pharmacodynamics, and Midazolam Drug Interaction in Healthy Volunteers
Ajay Madan, Yun Fei Zhu, Stacy Markison, Stephen F. Betz, Alan Krasner, Rosa Luo, Tilman Oltersdorf, Theresa Jochelson, Jason Lickliter, R. Scott Struthers. ENDO 2019. March 23-26, 2019; New Orleans.


2018

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.