Category: 478646-32-1

Franco, Francisco M. published the artcileStructure-based discovery of small molecule hepsin and HGFA protease inhibitors: Evaluation of potency and selectivity derived from distinct binding pockets, Computed Properties of 478646-32-1, the main research area is structure hepsin HGFA protease inhibitor; Benzamidine; Cancer; Cell-signaling; Enzyme inhibitor; Growth factor; HGF; HGFA; Hepsin; MSP; Matriptase; Peptidomimetic; RON; Receptor tyrosine kinase; Serine protease; Small-molecule; Structure-based drug design; Therapeutic; c-MET.

Hepatocyte growth factor activator (HGFA), matriptase and hepsin are all S1 trypsin-like serine endopeptidases. HGFA is a plasma protease while hepsin and matriptase are type II transmembrane proteases (TTSPs). Upregulated expression and activity of all three proteases is associated with aberrant cancer cell signaling through c-MET and RON tyrosine kinase cell-signaling pathways in cancer. The authors modeled known benzamidine protease inhibitor scaffolds into the active sites of matriptase, hepsin and HGFA to design new nonpeptide inhibitors of hepsin and HGFA. First, the authors used a docking model of the irreversible inhibitor, Nafamostat, bound to the active site of HGFA in order to explore structure activity relationships (SAR). Compounds were screened for inhibition of HGFA activity in a kinetic enzyme assay using a chromogenic substrate. Next, the authors designed matched pair compound libraries of 3-amidino and 4-amidino phenylalanine (benzamidine) arginine peptidomimetics based on the structure of matriptase inhibitor, CJ-672. Compounds were screened for inhibition of HGFA, matriptase, and hepsin enzyme activity using fluorogenic substrates. Using this strategy the authors have discovered the first reported nonpeptide small mol. inhibitors of both HGFA and hepsin. These inhibitors have differential potency and selectivity towards all three proteases. A subset of piperazinyl ureas highlighted by I, have excellent potency and selectivity for hepsin over matriptase and HGFA.

Bioorganic & Medicinal Chemistry published new progress about Homo sapiens. 478646-32-1 belongs to class piperidines, name is (R)-Benzyl piperidin-3-ylcarbamate, and the molecular formula is C13H18N2O2, Computed Properties of 478646-32-1.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Watterson, Scott H. published the artcileDiscovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton’s Tyrosine Kinase (BTK), Name: (R)-Benzyl piperidin-3-ylcarbamate, the main research area is covalent irreversible inhibitor Bruton’s tyrosine kinase Branebrutinib pharmacokinetics.

Bruton’s tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacol. inhibition of BTK is anticipated to provide an effective strategy for the clin. treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clin. studies.

Journal of Medicinal Chemistry published new progress about Bruton tyrosine kinase inhibitors (a covalent, irreversible inhibitor). 478646-32-1 belongs to class piperidines, name is (R)-Benzyl piperidin-3-ylcarbamate, and the molecular formula is C13H18N2O2, Name: (R)-Benzyl piperidin-3-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem