pp 17

Potent, selective peptide agonist for the neuropeptide Y Y5 receptor (IC50 values for inhibition of NPY binding to human Y5, Y1, Y2 and Y4 receptors are 0.24, 530, > 500, and 51 nM respectively, Ki at Y5 = 0.1 - 0.15 nM). Stimulates food intake in vivo.

L-685458 (L-685,458) 是一种过渡状态模拟 γ-分泌酶抑制剂，抑制淀粉样 β-蛋白前体 γ-分泌酶活性，选择性高于其他检测的天冬氨酸蛋白酶 50-100 倍。它抑制 γ-分泌酶介导的 APP-C99 和 Notch-100 的裂解，可研究阿尔茨海默病和癌症。

GNE-3500 is a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist. Retinoic acid receptor-related orphan receptor C (RORc, RORγ, or NR1F3) is a nuclear receptor that plays a major role in the production of interleukin (IL)-17. Considerable efforts have been directed toward the discovery of selective RORc inverse agonists as potential treatments of inflammatory diseases such as psoriasis and rheumatoid arthritis. GNE-3500 possessed favorable RORc cellular potency with 75-fold selectivity for RORc over other ROR family members and >200-fold selectivity over 25 additional nuclear receptors in a cell assay panel. The favorable potency, selectivity, in vitro ADME properties, in vivo PK, and dose-dependent inhibition of IL-17 in a PK PD model support the evaluation of GNE3500 in preclinical studies (J. Med. Chem., 2015, 58 (13), pp 5308–5322)