JAK1/2 ligand 1

JAK1/2 ligand 1 is a ligand for the PROTAC target protein of JAK1/2, which can be used to synthesize PROTAC JAK1/2 degrader-1. JAK1/2 ligand 1 is applicable to the research of colitis ^[1].

In Vivo, JAK1/2 ligand 1 (compound 8b) (40 mg/kg; p.o.; daily; 7 days) provides mild protective effects against DSS-induced colitis in C57BL/6 mice^[1].

In Vitro, JAK1/2 ligand 1 (compound 8b) (1.5 μM) does not induce JAK1 degradation in LPS-stimulated Raw 264.7 cells, either alone or in combination with Pomalidomide ^[1]. JAK1/2 ligand 1 (0.469-60 μM; 24 h) exhibits a favorable cellular safety profile in LPS-stimulated Raw 264.7 cells, showing no significant cytotoxicity within the tested concentration range^[1]. JAK1/2 ligand 1 (0.469-60 μM; 24 h) exhibits only weak inhibitory activity against LPS-induced NO production^[1]. AK1/2 ligand 1 (0.94-60 μM; 24 h) promotes JAK2 degradation in LPS-stimulated RAW 264.7 cells^[1]. JAK1/2 ligand 1 (0.05-60 μM; 24 h) shows weaker inhibitory activity against LPS-induced TNF-α and IL-6 secretion^[1]. JAK1/2 ligand 1 (0.029-3.75 μM; 24 h) suppresses LPS-induced NO, IL-6, and TNF-α production in a dose-dependent manner in Raw 264.7 cells and is non-cytotoxic at concentrations up to 3.75 μM^[1].

References:
[1]. Li G, et al. Development of potent JAK1/2 PROTAC degraders for the treatment of inflammatory bowel diseases. European journal of medicinal chemistry. 2026 Jan 15;302(Pt 3):118374.