The main purpose of this study in healthy participants is to learn more about the safety of LY3522348 and any side effects that might be associated with it. Blood tests will be performed to check how much LY3522348 gets into the bloodstream and how long it takes the body to eliminate it. This study has two parts: Part A will last up to about six weeks and Part B will last up to about eight weeks for each participant.

开始日期2020-10-15

申办/合作机构

Eli Lilly & Co.

100 项与 LY-3522348 相关的临床结果

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100 项与 LY-3522348 相关的转化医学

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100 项与 LY-3522348 相关的专利（医药）

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项与 LY-3522348 相关的文献（医药）

2024-11-01·Bioorganic & Medicinal Chemistry Letters

Discovery of BI-9787, a potent zwitterionic ketohexokinase inhibitor with oral bioavailability

Article

Fructose metabolism by ketohexokinase (KHK) is implicated in a variety of metabolic disorders. KHK inhibition is a potential therapeutic strategy for the treatment of diseases including diabetes, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis. The first small-molecule KHK-inhibitors have entered clinical trials, but it remains unclear if systemic inhibition of KHK by small-molecules will eventually benefit patients. Here we report the discovery of BI-9787, a potent, zwitterionic KHK inhibitor characterized by high permeability and favorable oral rat pharmacokinetics. BI-9787 was identified by optimizing chemical starting points generated via a ligand-based virtual screening of Boehringer's virtual library of synthetically accessible compounds (BICLAIM). It serves as a high-quality in vitro and in vivo tool compound for investigating the role of fructose metabolism in disease.

2023-12-14·Journal of Medicinal Chemistry1区 · 医学

Identification of LY3522348: A Highly Selective and Orally Efficacious Ketohexokinase Inhibitor

1区 · 医学

Article

作者: Antonellis, Meghan ; Durbin, Jim ; Mbofana, Curren T ; Massey, Steven ; Linder, Ryan J ; Lineswala, Jayana P ; Yumibe, Nathan ; Wang, Wei ; Toth, James L ; Hao, Junliang ; Tung, Frances ; Mascaro, Bethany ; Guo, Sherry ; Mínguez, Jose Miguel ; Johnston, Richard D ; Smith, Daryl L ; Durham, Timothy B ; MacKrell, James ; Lamar, Jason ; Perez, Carlos ; Corkins, Christopher ; Spinazze, Patrick ; Wrobleski, Aaron ; Leon, Rebecca ; Stack, Douglas R

The identification of clinical candidate LY3522348 (compound 23) is described. LY3522348 is a highly selective, oral dual inhibitor of human ketohexokinase isoforms C and A (hKHK-C, hKHK-A). Optimization began with highly efficient (S)-2-(2-methylazetidin-1-yl)-6-(1H-pyrazol-4-yl)-4-(trifluoromethyl)nicotinonitrile (3). Efforts focused on developing absorption, distribution, metabolism, potency, and in vitro safety profiles to support oral QD dosing in patients. Structure-based design leveraged vectors for substitution of the pyrazole ring, which provided an opportunity to interact with several different proximal amino acid residues in the protein. LY3522348 displayed a robust pharmacodynamic response in a mouse model of fructose metabolism and was advanced into clinical trials.

Journal of Medicinal Chemistry

Identification of LY3522348: A Highly Selective and Orally Efficacious Ketohexokinase (KHK) Inhibitor

作者: MacKrell, James ; Mascaro, Bethany ; Linder, Ryan J. ; Massey, Steven ; Yumibe, Nathan ; Stack, Douglas R. ; Mbofana, Curren T. ; Hao, Junliang ; Corkins, Christopher ; Minguez, Jose Miguel ; Durham, Timothy B. ; Smith, Daryl L. ; Toth, James L. ; Guo, Sherry ; Johnston, Richard D. ; Lamar, Jason ; Spinazze, Patrick ; Wang, Wei ; Leon, Rebecca ; Antonellis, Meghan ; Lineswala, Jayana P. ; Durbin, Jim ; Perez, Carlos ; Wrobleski, Aaron ; Tung, Frances

The identification of clin. candidate LY3522348 (compound 23) is described.LY3522348 is a highly selective, oral dual inhibitor of human ketohexokinase isoforms C and A (hKHK-C, hKHK-A).Optimization began with highly efficient (S)-2-(2-methylazetidin-1-yl)-6-(1H-pyrazol-4-yl)-4-(trifluoromethyl)nicotinonitrile (3).Efforts focused on developing absorption, distribution, metabolism, potency and in vitro safety profiles to support oral QD dosing in patients.Structure based design leveraged vectors for substitution off the pyrazole ring, which provided opportunity to interact with several different proximal amino acid residues in the protein.LY3522348 displayed robust pharmacodynamic response in a mouse model of fructose metabolism and was advanced into clin. trials.

100 项与 LY-3522348 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
糖尿病	临床前	美国	Eli Lilly & Co.	-
心脏衰竭	临床前	美国	Eli Lilly & Co.	-
肾脏疾病	临床前	美国	Eli Lilly & Co.	-
非酒精性脂肪性肝炎	临床前	美国	Eli Lilly & Co.	-