An article Identification of N-Methyl Nicotinamide and N-Methyl Pyridazine-3-Carboxamide Pseudokinase Domain Ligands as Highly Selective Allosteric Inhibitors of Tyrosine Kinase 2 (TYK2) WOS:000492801800005 published article about MONOCLONAL-ANTIBODY; POTENT; ACTIVATION; MODERATE; SIGNAL; ROLES; OPTIMIZATION; USTEKINUMAB; MOLECULES; DISCOVERY in [Moslin, Ryan; Zhang, Yanlei; Wrobleski, Stephen T.; Lin, Shuqun; Mertzman, Michael; Spergel, Steven; Lombardo, Louis; Carter, Percy H.; Weinstein, David S.] Bristol Myers Squibb Res & Dev, Immunosci Discovery Chem, POB 4000, Princeton, NJ 08543 USA; [Strnad, Joann; Gillooly, Kathleen; McIntyre, Kim W.; Zupa-Fernandez, Adriana; Cheng, Lihong; Heimrich, Elizabeth; Yang, Xiaoxia; Burke, James R.] Bristol Myers Squibb Res & Dev, Immunosci Discovery Biol, POB 4000, Princeton, NJ 08543 USA; [Tokarski, John S.; Muckelbauer, Jodi K.; Chang, ChiehYing; Tredup, Jeffrey; Mulligan, Dawn; Xie, Dianlin] Bristol Myers Squibb Res & Dev, Mol Struct & Design, Mol Discovery Technol, POB 4000, Princeton, NJ 08543 USA; [Sun, Huadong; Huang, Christine; D’Arienzo, Celia; Aranibar, Nelly; Chiney, Manoj] Bristol Myers Squibb Res & Dev, Lead Discovery & Optimizat, POB 4000, Princeton, NJ 08543 USA; [Chaudhry, Charu] Bristol Myers Squibb Res & Dev, Metab & Pharmacokinet Dept, Pharmaceut Candidate Optimizat, POB 4000, Princeton, NJ 08543 USA; [Weinstein, David S.] Vividion Therapeut Inc, Chem, 5820 Nancy Ridge Dr, San Diego, CA 92121 USA in 2019, Cited 53. The Name is 2-Aminobenzamide. Through research, I have a further understanding and discovery of 88-68-6. Safety of 2-Aminobenzamide
As a member of the Janus OAK) family of nonreceptor tyrosine kinases, TYK2 plays an important role in mediating the signaling of pro-inflammatory cytokines including IL-12, IL-23, and type 1 interferons. The nicotinamide 4, identified by a SPA-based high-throughput screen targeting the TYK2 pseudokinase domain, potently inhibits IL-23 and IFN alpha signaling in cellular assays. The described work details the optimization of this poorly selective hit (4) to potent and selective molecules such as 47 and 48. The discoveries described herein were critical to the eventual identification of the clinical TYK2 JH2 inhibitor (see following report in this issue). Compound 48 provided robust inhibition in a mouse IL-12-induced IFN gamma pharmacodynamic model as well as efficacy in an IL-23 and IL-12-dependent mouse colitis model. These results demonstrate the ability of TYK2 JH2 domain binders to provide a highly selective alternative to conventional TYK2 orthosteric inhibitors.
Safety of 2-Aminobenzamide. About 2-Aminobenzamide, If you have any questions, you can contact Moslin, R; Zhang, YL; Wrobleski, ST; Lin, SQ; Mertzman, M; Spergel, S; Tokarski, JS; Strnad, J; Gillooly, K; McIntyre, KW; Zupa-Fernandez, A; Cheng, LH; Sun, HD; Chaudhry, C; Huang, C; D’Arienzo, C; Heimrich, E; Yang, XX; Muckelbauer, JK; Chang, C; Tredup, J; Mulligan, D; Xie, DL; Aranibar, N; Chiney, M; Burke, JR; Lombardo, L; Carter, PH; Weinstein, DS or concate me.
Reference:
Thiomorpholine – Wikipedia,
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