NAMPT/IDO1-IN-1

NAMPT/IDO1-IN-1 is an orally active dual inhibitor of NAMPT and IDO1 with IC50s of 57.7 nM and 233 nM, respectively. NAMPT/IDO1-IN-1 blocks NAD+ biosynthesis, inhibits proliferation and migration of Paclitaxel (HY-B0015)- and FK866 (HY-50876)-resistant NSCLC cell lines (A549/R cells). NAMPT/IDO1-IN-1 has shown antitumor effects in mice and enhanced A549/R cell sensitivity to paclitaxel[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Indoleamine 2,3-Dioxygenase (IDO)

Signaling Pathways >> Metabolic Enzyme/Protease >> Nampt

IDO1:233 nM (IC50)

NAMPT:57.7 nM (IC50)

NAMPT/IDO1-IN-1 (化合物 10e) (10 μM; 48 h) 对 A549/R 细胞具有抗增殖活性，并依赖于 NAMPT 和 IDO1[1]。 NAMPT/IDO1-IN-1 (5 μM, 10 μM, 15 μM; 12 d) 抑制 A549/R 细胞的集落形成，并以剂量依赖的方式促进细胞内 ROS 的积累[1]。 NAMPT/IDO1-IN-1 (10 μM; 24 h) 以 NAMPT 和 IDO1 依赖的方式减少 A549/R 细胞中的 NAD+[1]。

NAMPT/IDO1-IN-1 (化合物 10e) (5 μM; 24 h) 对斑马鱼胚胎的 ROS 有促进作用，其 ROS 水平远高于 LPS (50 μg/mL) 处理[1]。 NAMPT/IDO1-IN-1 (25 mg/kg; 口服; 单次剂量) 具有良好的口服生物利用度和 (5 mg/kg; 静脉注射; 单次剂量) 显示出中等整体暴露度[1]。 NAMPT/IDO1-IN-1 (50、100、200 mg/kg; 口服; 每天 2 次, 共 3 周) 在 A549/R 肿瘤异种移植模型中也显示出体内抗肿瘤作用[1]。 Animal Model: Female nude 6-8 week old mice with A549/R cells[1] Dosage: 50, 100, and 200 mg/kg Administration: Oral gavage; twice daily for 3 weeks Result: Showed much better inhibitory activity against A549/R xenografts compared with the single agent. Showed comparable anti-tumor efficacy with the combination of FK866 and epacadostat at dose of 100 mg/kg, while at 200 mg/kg showed better efficacy than the combination group.

[1]. Wang K, et al. Dual Nicotinamide Phosphoribosyltransferase (NAMPT) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors for the Treatment of Drug-Resistant Nonsmall-Cell Lung Cancer. J Med Chem. 2023 Jan 12;66(1):1027-1047.