Category: 292170-96-8

Norton, David published the artcileFragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction, Name: 5-Bromo-N,N-dimethylnicotinamide, the main research area is pyrazole carboxylic acid inhibitor KEAP1 NRF2 protein interaction.

The NRF2-mediated cytoprotective response is central to cellular homeostasis, and there is increasing interest in developing small-mol. activators of this pathway as therapeutics for diseases involving chronic oxidative stress. The protein KEAP1, which regulates NRF2, is a key point for pharmacol. intervention, and we recently described the use of fragment-based drug discovery to develop a tool compound that directly disrupts the protein-protein interaction between NRF2 and KEAP1. We now present the identification of a second, chem. distinct series of KEAP1 inhibitors, which provided an alternative chemotype for lead optimization. Pharmacophoric information from our original fragment screen was used to identify new hit matter through database searching and to evolve this into a new lead with high target affinity and cell-based activity. We highlight how knowledge obtained from fragment-based approaches can be used to focus addnl. screening campaigns in order to de-risk projects through the rapid identification of novel chem. series.

Journal of Medicinal Chemistry published new progress about Drug design. 292170-96-8 belongs to class amides-buliding-blocks, name is 5-Bromo-N,N-dimethylnicotinamide, and the molecular formula is C8H9BrN2O, Name: 5-Bromo-N,N-dimethylnicotinamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Hoyt, Scott B. published the artcileDiscovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys, Computed Properties of 292170-96-8, the main research area is triazole preparation aldosterone synthase inhibitor; Aldosterone synthase; CYP11B2; hit-to-lead; hypertension.

Hit-to-lead efforts resulted in the discovery of compound I, a potent CYP11B2 inhibitor that displays high selectivity vs. related CYPs, good pharmacokinetic properties in rat and rhesus, and lead-like phys. properties. In a rhesus pharmacodynamic model, compound I displays robust, dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.

ACS Medicinal Chemistry Letters published new progress about Aldosteronism. 292170-96-8 belongs to class amides-buliding-blocks, name is 5-Bromo-N,N-dimethylnicotinamide, and the molecular formula is C8H9BrN2O, Computed Properties of 292170-96-8.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Quach, David published the artcileStrategic Design of Catalytic Lysine-Targeting Reversible Covalent BCR-ABL Inhibitors, HPLC of Formula: 292170-96-8, the main research area is BCR ABL inhibitor lysine drug design; cancer; covalent inhibitors; lysine; proteomics; reversibility.

Targeted covalent inhibitors have re-emerged as validated drugs to overcome acquired resistance in cancer treatment. Herein, by using a carbonyl boronic acid (CBA) warhead, we report the structure-based design of BCR-ABL inhibitors via reversible covalent targeting of the catalytic lysine with improved potency against both wild-type and mutant ABL kinases, especially ABLT315I bearing the gatekeeper residue mutation. We show the evolutionarily conserved lysine can be targeted selectively, and the selectivity depends largely on mol. recognition of the non-covalent pharmacophore in this class of inhibitors, probably due to the moderate reactivity of the warhead. We report the first co-crystal structures of covalent inhibitor-ABL kinase domain complexes, providing insights into the interaction of this warhead with the catalytic lysine. We also employed label-free mass spectrometry to evaluate off-targets of our compounds at proteome-wide level in different mammalian cells.

Angewandte Chemie, International Edition published new progress about Antiproliferative agents. 292170-96-8 belongs to class amides-buliding-blocks, name is 5-Bromo-N,N-dimethylnicotinamide, and the molecular formula is C8H9BrN2O, HPLC of Formula: 292170-96-8.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics