Discovery of the first Mycobacterium tuberculosis MabA (FabG1) inhibitors through a fragment-based screening.
Sign Up to like & getrecommendations! Published in 2020 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2020.112440
Abstract: Mycobacterium tuberculosis (M.tb), the etiologic agent of tuberculosis, remains the leading cause of death from a single infectious agent worldwide. The emergence of drug-resistant M.tb strains stresses the need for drugs acting on new targets.… read more here.
Keywords: maba; tuberculosis; discovery first; maba fabg1 ... See more keywords
Discovery of the First Examples of Threonine Tyrosine Kinase PROTAC Degraders.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c01768
Abstract: The first examples of threonine tyrosine kinase (TTK) PROTACs were designed and synthesized. Two of the most potent molecules, 8e and 8j, demonstrated strong TTK degradation in COLO-205 human colorectal cancer cells with DC50 values… read more here.
Keywords: first examples; threonine tyrosine; tyrosine kinase; examples threonine ... See more keywords
Discovery of the First-in-Class Agonist-Based SOS1 PROTACs Effective in Human Cancer Cells Harboring Various KRAS Mutations.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c01774
Abstract: Regulating SOS1 functions may result in targeted pan-KRAS therapies. Small-molecule SOS1 inhibitors showed promising anticancer potential, and the most advanced inhibitor BI 1701963 is currently under phase I clinical studies. SOS1 agonists provide new opportunities… read more here.
Keywords: cancer; agonist; sos1 protacs; discovery first ... See more keywords
Discovery of the First Selective IDO2 Inhibitor As Novel Immunotherapeutic Avenues for Rheumatoid Arthritis.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00263
Abstract: Indoleamine 2,3-dioxygenase 2 (IDO2), a closely related homologue of well-studied immunomodulatory enzyme IDO1, has been identified as a pathogenic mediator of inflammatory autoimmunity in preclinical models. Therapeutic targeting IDO2 in autoimmune diseases has been challenging… read more here.
Keywords: inhibitor; arthritis; ido2; ido2 inhibitor ... See more keywords
Discovery of the First-in-Class G9a/GLP Covalent Inhibitors.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00652
Abstract: The highly homologous protein lysine methyltransferases G9a and GLP, which catalyze mono- and dimethylation of histone H3 lysine 9 (H3K9), have been implicated in various human diseases. To investigate functions of G9a and GLP in… read more here.
Keywords: glp; discovery first; first class; covalent ... See more keywords
Discovery of the First Subnanomolar PPARα/δ Dual Agonist for the Treatment of Cholestatic Liver Diseases.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c02123
Abstract: Peroxisome proliferator-activator receptors α/δ (PPARα/δ) are considered as potential drug targets for cholestatic liver diseases (CLD) via ameliorating hepatic cholestasis, inflammation, and fibrosis. In this work, we developed a series of hydantoin derivatives as potent… read more here.
Keywords: ppar; ppar dual; liver diseases; discovery first ... See more keywords
Discovery of the First Potent, Selective, and Orally Bioavailable Signal Peptide Peptidase-Like 2a (SPPL2a) Inhibitor Displaying Pronounced Immunomodulatory Effects In Vivo.
Sign Up to like & getrecommendations! Published in 2018 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.7b01371
Abstract: Signal peptide peptidase-like 2a (SPPL2a) is an aspartic intramembrane protease which has recently been shown to play an important role in the development and function of antigen presenting cells such as B lymphocytes and dendritic… read more here.
Keywords: sppl2a; signal peptide; peptidase like; discovery first ... See more keywords
Discovery of a First-in-class Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Degrader.
Sign Up to like & getrecommendations! Published in 2019 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.9b01528
Abstract: MEK1 and MEK2 (also known as MAP2K1 and MAP2K2) are the "gatekeepers" of the ERK signaling output with redundant roles in controlling ERK activity. Numerous inhibitors targeting MEK1/2 have been developed including three FDA-approved drugs.… read more here.
Keywords: degrader; kinase; discovery first; mek1 ... See more keywords
From proteomics to discovery of first-in-class ST2 inhibitors active in vivo.
Sign Up to like & getrecommendations! Published in 2018 at "JCI insight"
DOI: 10.1172/jci.insight.99208
Abstract: Soluble cytokine receptors function as decoy receptors to attenuate cytokine-mediated signaling and modulate downstream cellular responses. Dysregulated overproduction of soluble receptors can be pathological, such as soluble ST2 (sST2), a prognostic biomarker in cardiovascular diseases,… read more here.
Keywords: vivo; st2 inhibitors; discovery first; proteomics discovery ... See more keywords
Genome-Guided Discovery of the First Myxobacterial Biarylitide Myxarylin Reveals Distinct C–N Biaryl Crosslinking in RiPP Biosynthesis
Sign Up to like & getrecommendations! Published in 2021 at "Molecules"
DOI: 10.3390/molecules26247483
Abstract: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse group of natural products. They feature a wide range of intriguing post-translational modifications, as exemplified by the biarylitides. These are a family of cyclic… read more here.
Keywords: guided discovery; myxarylin; biarylitide; biaryl ... See more keywords