Dietrich, Justin D.; Longenecker, Kenton L.; Wilson, Noel S.; Goess, Christian; Panchal, Sanjay C.; Swann, Steven L.; Petros, Andrew M.; Hobson, Adrian D.; Ihle, David; Song, Danying; Richardson, Paul; Comess, Kenneth M.; Cox, Philip B.; Dombrowski, Amanda; Sarris, Kathy; Donnelly-Roberts, Diana L.; Duignan, David B.; Gomtsyan, Arthur; Jung, Paul; Krueger, A. Chris; Mathieu, Suzanne; McClure, Andrea; Stoll, Vincent S.; Wetter, Jill; Mankovich, John A.; Hajduk, Philip J.; Vasudevan, Anil; Stoffel, Robert H.; Sun, Chaohong published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Development of Orally Efficacious Allosteric Inhibitors of TNFα via Fragment-Based Drug Design》.HPLC of Formula: 89466-08-0 The article contains the following contents:
Tumor necrosis factor α (TNFα) is a soluble cytokine that is directly involved in systemic inflammation through the regulation of the intracellular NF-κB and MAPK signaling pathways. The development of biol. drugs that inhibit TNFα has led to improved clin. outcomes for patients with rheumatoid arthritis and other chronic autoimmune diseases; however, TNFα has proven to be difficult to drug with small mols. Herein, we present a two-phase, fragment-based drug discovery (FBDD) effort in which we first identified isoquinoline fragments that disrupt TNFα ligand-receptor binding through an allosteric desymmetrization mechanism as observed in high-resolution crystal structures. The second phase of discovery focused on the de novo design and optimization of fragments with improved binding efficiency and drug-like properties. The 3-indolinone-based lead compound 12 (I) presented here displays oral, in vivo efficacy in a mouse glucose-6-phosphate isomerase (GPI)-induced paw swelling model comparable to that seen with a TNFα antibody. In the experimental materials used by the author, we found 2-Hydroxyphenylboronic acid(cas: 89466-08-0HPLC of Formula: 89466-08-0)
2-Hydroxyphenylboronic acid(cas: 89466-08-0) belongs to acyl phenylboronic acid. Phenylboronic acid (PBA) has been used to extract β-blockers (a class of aminoalcohol-containing drugs) from aqueous solution, rat, and human plasma. HPLC of Formula: 89466-08-0
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts