YL5084

YL5084, a covalent JNK inhibitor, exhibits selectivity for JNK2 and JNK3 over JNK1 with IC50s of 70 nM, 84 nM and 2173 nM, respectively. YL5084 exhibits JNK2-independent antiproliferative effects and induces apoptosis in a JNK2-independent manner[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> MAPK/ERK Pathway >> JNK

JNK2:70 nM (IC50)

JNK3:84 nM (IC50)

JNK1:2173 nM (IC50)

YL5084 (0.001-100 μM; 72 小时) 在 MM.1S 细胞中表现出剂量依赖性抗增殖作用，GR50 值为 200-300 nM[1]。 YL5084 (0.5, 2.5 μM; 24 小时) 诱导细胞凋亡[1]。 YL5084 对 PIKFYVE (KdELECT 结合测定中的 KD=5000 nM) 表现出较弱的抑制作用[1]。 YL5084 在人和小鼠微粒体中具有中等代谢稳定性，半衰期分别为 16 分钟和 11 分钟[1]。 Cell Proliferation Assay[1] Cell Line: Multiple myeloma (MM) cell lines Concentration: 0.001-100 μM Incubation Time: 72 h Result: Displayed dose-dependent antiproliferative effects with GR50 values of 200-300 nM. Apoptosis Analysis[1] Cell Line: MM.1S cells Concentration: 0.5, 2.5 μM Incubation Time: 24 h Result: Induced apoptosis as evidenced by an increased level of PARP cleavage, an increased level of cleavage of caspase 3, and an increased level of Annexin V/PI staining.

[1]. Wenchao Lu, et al. Development of a Covalent Inhibitor of c-Jun N-Terminal Protein Kinase (JNK) 2/3 with Selectivity over JNK1. J Med Chem. 2023 Mar 9;66(5):3356-3371.