Category: 960388-56-1

Kornecook, Thomas J. published the artcilePharmacologic characterization of AMG8379, a potent and selective small molecule sulfonamide antagonist of the voltage-gated sodium channel NaV1.7, Quality Control of 960388-56-1, the publication is Journal of Pharmacology and Experimental Therapeutics (2017), 362(1), 146-160, database is CAplus and MEDLINE.

Potent and selective antagonists of the voltage-gated sodium channel NaV1.7 represent a promising avenue for the development of new chronic pain therapies. We generated a small mol. atropisomer quinolone sulfonamide antagonist AMG8379 and a less active enantiomer AMG8380. Here we show that AMG8379 potently blocks human NaV1.7 channels with an IC50 of 8.5 nM and endogenous tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglion (DRG) neurons with an IC50 of 3.1 nM in whole-cell patch clamp electrophysiol. assays using a voltage protocol that interrogates channels in a partially inactivated state. AMG8379 was 100- to 1000-fold selective over other NaV family members, including NaV1.4 expressed in muscle and NaV1.5 expressed in the heart, as well as TTX-resistant NaV channels in DRG neurons. Using an ex vivo mouse skin-nerve preparation, AMG8379 blocked mech. induced action potential firing in C-fibers in both a time-dependent and dose-dependent manner. AMG8379 similarly reduced the frequency of thermally induced C-fiber spiking, whereas AMG8380 affected neither mech. nor thermal responses. In vivo target engagement of AMG8379 in mice was evaluated in multiple NaV1.7-dependent behavioral endpoints. AMG8379 dose-dependently inhibited intradermal histamine-induced scratching and intraplantar capsaicin-induced licking, and reversed UVB radiation skin burn-induced thermal hyperalgesia; notably, behavioral effects were not observed with AMG8380 at similar plasma exposure levels. AMG8379 is a potent and selective NaV1.7 inhibitor that blocks sodium current in heterologous cells as well as DRG neurons, inhibits action potential firing in peripheral nerve fibers, and exhibits pharmacodynamic effects in translatable models of both itch and pain.

Journal of Pharmacology and Experimental Therapeutics published new progress about 960388-56-1. 960388-56-1 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Phenol,Boronate Esters,Boronic Acids,Boronic acid and ester,Boronate Esters, name is 3-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, and the molecular formula is C12H16BClO3, Quality Control of 960388-56-1.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

He, Xiaohui published the artcileIdentification of Potent and Selective RIPK2 Inhibitors for the Treatment of Inflammatory Diseases, Recommanded Product: 3-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, the publication is ACS Medicinal Chemistry Letters (2017), 8(10), 1048-1053, database is CAplus and MEDLINE.

NOD2 (nucleotide-binding oligomerization domain-containing protein 2) is an internal pattern recognition receptor that recognizes bacterial peptidoglycan and stimulates host immune responses. Dysfunction of NOD2 pathway has been associated with a number of autoinflammatory disorders. To date, direct inhibitors of NOD2 have not been described due to tech. challenges of targeting the oligomeric protein complex. Receptor interacting protein kinase 2 (RIPK2) is an intracellular serine/threonine/tyrosine kinase, a key signaling partner, and an obligate kinase for NOD2. As such, RIPK2 represents an attractive target to probe the pathol. roles of NOD2 pathway. To search for selective RIPK2 inhibitors, the authors employed virtual library screening (VLS) and structure based design that eventually led to a potent and selective RIPK2 inhibitor 8 (4-(7-ethoxy-6-(isopropylsulfonyl)imidazo[1,2-a]pyridin-3-yl)-6-fluoropyridin-2-amine) with excellent oral bioavailability, which was used to evaluate the effects of inhibition of RIPK2 in various in vitro assays and ex vivo and in vivo pharmacodynamic models.

ACS Medicinal Chemistry Letters published new progress about 960388-56-1. 960388-56-1 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Phenol,Boronate Esters,Boronic Acids,Boronic acid and ester,Boronate Esters, name is 3-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, and the molecular formula is C12H16BClO3, Recommanded Product: 3-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics