Effector Therapeutics, Inc.

Itherx Pharmaceuticals Inc.

Yale University

Lycia Therapeutics, Inc.

Justin T Ernst

Paul A Sprengeler

Siegfried Heinz Reich

Alan X Xiang

Stephen Evan Webber

Chinh Viet Tran

Garrick Kenneth Packard

Samuel Sperry

Theo Michels

Christian Nilewski

Robert W Sullivan

Antonio Garrido Montalban

Edward Roberts

Christopher Larson

Russell Dahl

Hiroshi Nakanishi

Jeffrey Dean Kahl

Erik Boman

Susana Conde Ceide

Nancy G J Delaet

Eddine Saiah

Zhinjun Wang

Andrew D Hamilton

Bennett C Borer

Stephen F Miller

Jo Ann Z Wilson

Mike Shaghafi

Brendan Orner

Jason Gustaf Lewis

Eric Douglas Turtle

Brett Bradley Busch

Kaveri Urkalan

Douglas Murphy

Alan Grubbs

Seigfried H Reich

Takasuke Mukaiyama

Chinh Tran

Theodore Michels

Siegfried H Reich

Alan Xin Xiang

The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface asialoglycoprotein receptor (ASGPR). The cell surface ASGPR binding compounds can trigger the receptor to internalize into the cell a bound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor ASGPR. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided herein methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.

ASGPR cell surface receptor binding compounds and conjugates

The present invention provides crystalline solids of 6′-((6-aminopyrimidin-4-yl)amino)-8′-methyl-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione: The crystalline compounds of the present application are inhibitors of Mnk and finds utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Crystalline forms of Mnk inhibitors

The present invention relates to compounds according to Formula (I): or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof wherein X, X, R, R, Rand n are as defined herein. Also described are pharmaceutically acceptable compositions of Formula (I) compounds as well as methods for utilizing the compounds of Formula (I) and the pharmaceutically acceptable compositions of Formula (I) compounds as inhibitors of Mnk as well as therapeutics for the treatment of diseases such as cancer.

Piperidine-substituted Mnk inhibitors and methods related thereto

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.  For Formula I compounds X, Y, R, R, R, R, R, Rand Rare as defined in the specification. The inventive Formula I compounds are inhibitors of eIF4A and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

EIF4A-inhibiting compounds and methods related thereto

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.  For Formula I compounds X, X, X, X, X, X, Q, L, L, Y, R, R, R, R, R, R, R, Rand rings A, B and C are as defined in the specification. The inventive Formula I compounds are inhibitors of eIF4e and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

EIF4E-inhibiting compounds and methods

The present invention provides crystalline solids of 6'-((6-aminopyrimidin-4-yl)amino)-8&#x2032;-methyl-2&#x2032;H-spiro[cyclohexane-1,3&#x2032;-imidazo[1,5-a]pyridine]-1&#x2032;,5&#x2032;-dione: The crystalline compounds of the present application are inhibitors of Mnk and finds utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Crystalline forms of MNK inhibitors

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I. or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. For Formula I compounds A, A. A, A, A, A, A, W, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, Rand Rand subscripts 'm' and 'n' are as defined in the specification. The inventive Formula I compounds are inhibitors of Mnk and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Pyrrolo-, pyrazolo-, imidazo-pyrimidine and pyridine compounds that inhibit MNK1 and MNK2

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I or Formula II, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. For Formula I compounds X, X, X, X, X, Y, Y, R, R, R, R, R, R, R, R, R, R, R, Rand Rare as defined in the specification. The inventive Formula I and Formula II compounds are inhibitors of Mnk and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Benzimidazole-indole inhibitors of Mnk1 and Mnk2

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. For Formula I compounds X, Y, R, R, R, R, R, Rand Rare as defined in the specification. The inventive Formula I compounds are inhibitors of eIF4A and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. For Formula I compounds A, A, A, A, A, W, Y, R, R, R, R, R, R, R, R, R, R, R, R, R, R, and Rand subscript 'n' are as defined in the specification. The inventive Formula I compounds are inhibitors of Mnk and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Isoindoline, azaisoindoline, dihydroindenone and dihydroazaindenone inhibitors of Mnk1 and Mnk2

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula IA or Formula IB, as well as stereoisomers, tautomers or pharmaceutically acceptable salts thereof. For Formula IA and Formula IB compounds A, A, A, A, W, W, Y, X, R, R, R, R, R, R, R, R, R, R, R, R, R, Rand subscript n are as defined in the specification. The inventive Formula IA and Formula IB compounds are inhibitors of Mnk and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Heterocyclic compounds that inhibit the kinase activity of Mnk useful for treating various cancers

eIF4A-inhibiting compounds and methods related thereto

The present invention relates to compounds according to Formula (I): or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R, R, R, R, R, R, R, R, R, W, W, Y and n are as defined herein. Also described are pharmaceutically acceptable compositions of Formula I compounds as well as methods for utilizing the compounds of Formula I and the pharmaceutically acceptable compositions of Formula I compounds as inhibitors of Mnk as well as therapeutics for the treatment of diseases such as cancer.

MNK inhibitors and methods related thereto

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San Diego, CA, United States of America

Justin T Ernst