Peter Orth

Structure-Based Drug Design of Quinoline CYP8B1 Inhibitors for the Potential Treatment of Metabolic Disease

Amy Bittner McCracken, Derun Li, John P. Caldwell, Claire Lankin et autres

Abstract CYP8B1 has been identified as a potential target for the treatment of metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). CYP8B1 enzyme inhibitor 1 was discovered from a high-throughput screen of our compound collection; however, …

us (code pays fourni par la source)

Correction to “Discovery Process of Enlicitide, a Highly Engineered Macrocyclic Peptide Therapeutic, Through Issue Driven Fragment-Based Synthetic Assembly and SAR”

Hubert Josien, Anilkumar G. Nair, Fa‐Xiang Ding, Yan Guo et autres

Discovery Process of Enlicitide, a Highly Engineered Macrocyclic Peptide Therapeutic, through Issue-Driven Fragment-Based Synthetic Assembly and SAR

Hubert Josien, Anilkumar G. Nair, Fa‐Xiang Ding, Yan Guo et autres

Abstract Herein, we report the discovery process of enlicitide (MK-0616, compound 18), an orally active macrocyclic peptide therapeutic against PCSK9 for LDL-C reduction. To overcome development bottlenecks in a prior lead (compound 1a) in a timely manner (sulfur oxidation liability, low solubility, …

us (code pays fourni par la source)

Mirror-image mRNA display uncovers isoform-selective D-peptide macrocycles targeting a cryptic KRAS pocket

Matthew J. Mitcheltree, Nicole Boo, Nicolas Boyer, Zachary Z. Brown et autres

SUMMARY Activating KRAS mutations drive millions of cancers diagnosed worldwide, 1 yet for decades this oncoprotein was deemed “undruggable”, reflecting the challenge of discovering molecules capable of perturbing its complex biological functions, and of translating these discoveries into effective cancer therapeutics. 2 …

us, jp (code pays fourni par la source)