Merck Sharp + Dohme Corp.

Ra Pharmaceuticals, Inc.

Merck Sharpe & Dohme Corp.

Hyewon Youm

Hubert B Josien

Frank W Bennett

Yusheng Xiong

Angela Dawn Kerekes

Thomas Joseph Tucker

Elisabetta Bianchi

Raffaele Ingenito

Danila Branca

Chengwei Wu

Alonso Ricardo

Nicolas Cedric Boyer

Sookhee Nicole Ha

Aurash Shahripour

Jason Eugene Imbriglio

Willy Costantini

Zhijian Lu

Alessia Santoprete

Rui Liang

James R Tata

Eric J Gilbert

Zhong Ma

Mark W Embrey

Clare London

Ketki Ashok Dhamnaskar

Immacolata Conte

Stefania Colarusso

Joseph R Stringer

Derek M LaPlaca

Ming You

Roberto Costante

Zhicai Wu

Fa-Xiang Ding

Derun Li

Wonsuk Chang

Tanweer A Khan

Scott B Hoyt

Abbas M Walji

Pengcheng Patrick Shao

Feng Ye

Jerry Andrew Taylor

Claire Lankin

Yang Yu

Qingmei Hong

Whitney Lane Petrilli

Zhe Feng

Venukrishnan Komanduri

Anthappan Tony Kurissery

The present invention relates to Compounds of Formula I: and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment of cardiometabolic diseases including high blood pressure, heart failure, kidney disease, and diabetes in a subject.

Natriuretic peptide receptor a agonists useful for the treatment of cardiometabolic diseases, kidney disease and diabetes

Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.

Cyclic polypeptides for PCSK9 inhibition

Disclosed are compounds of Formula I, or a salt thereof cyclic polypeptide of Formula I: Formula I where A, B, E, R, and Rare as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions 

PCSK9 antagonists bicyclo-compounds

The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X, X, Y, R, R, R, Rand n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples. 

Substituted 1-methyl-1,2,3,4-tetrahydroisoquinoline molecules as PCSK9 allosteric binders

The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 ('DGAT2') and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardio renal diseases such as chronic kidney diseases and heart failure and related diseases and conditions. 

Tetrahydroisoquinoline derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2

The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 ('DGAT2') and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardio-renal diseases such as chronic kidney diseases and heart failure and related diseases and conditions. 

Isoquinoline derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2

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Berkeley Heights, NJ, United States of America

Hyewon Youm