ACS Medicinal Chemistry Letters最新文献

We report the first structure-activity studies of arylidene-indolinone compound GW5074, which was reported as a ligand of autophagy-related protein LC3B. The literature has conflicting information on the binding affinity of this compound, and there is some debate regarding its use as a component of autophagy-dependent degrader compounds. We developed an AlphaScreen assay to measure competitive inhibition of the binding of known peptide ligands to LC3B and its paralog GABARAP. Eighteen analogs were synthesized and tested against both proteins. Inhibitory potencies were found to be in the mid- to high-micromolar range. 2D-NMR data revealed the binding site on GABARAP as hydrophobic pocket 1, where native peptide ligands bind with an aromatic side chain. Our results suggest that GW5074 binds LC3B and GABARAP with micromolar affinity. These affinities could support further exploration in targeted protein degradation, but only if off-target effects and poor solubility can be appropriately addressed.

The invention described in this patent application relates to oral compounds represented by Formula I. These compounds are designed to specifically target and inhibit KRAS alleles, providing both therapeutic and prophylactic potential in mammals, particularly for the treatment of KRAS-driven cancers.

The invention in this patent describes novel 5H-imidazo[1,5-b][1,2,4]triazole compounds, including radiolabeled derivatives, designed to target alpha-synuclein (α-syn). These compounds demonstrate potential as positron emission tomography (PET) radioligands for diagnosing α-syn-associated brain diseases, including Parkinson's disease.

This patent application pertains to macrocyclic peptides and their radiolabeled derivatives, generally represented by Formula I. These compounds exhibit selective binding to Granzyme B (GzmB) and hold the potential for imaging disease or disorders associated with elevated GzmB levels. Such conditions include cancer immunotherapy, autoimmunity, wound healing, and inflammation.

This Patent Highlight describes novel substituted heterocyclic piperazine amide compounds and their isotopically labeled derivatives. These compounds are designed as promising positron emission tomography (PET) ligands targeting alpha-synuclein, offering potential for the diagnosis of neurodegenerative disorders, including Parkinson's disease.

This Patent Highlight describes novel substituted heterocyclic piperazine amide compounds and their isotopically labeled derivatives. These compounds are designed as promising positron emission tomography (PET) ligands targeting alpha-synuclein, offering potential for the diagnosis of neurodegenerative disorders, including Parkinson’s disease.

The invention described in this patent application relates to oral compounds represented by Formula I. These compounds are designed to specifically target and inhibit KRAS alleles, providing both therapeutic and prophylactic potential in mammals, particularly for the treatment of KRAS-driven cancers.

This patent application pertains to macrocyclic peptides and their radiolabeled derivatives, generally represented by Formula I. These compounds exhibit selective binding to Granzyme B (GzmB) and hold the potential for imaging disease or disorders associated with elevated GzmB levels. Such conditions include cancer immunotherapy, autoimmunity, wound healing, and inflammation.

Provided herein are novel 3-cycloaminoindole compounds as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders and processes for preparing such compounds.