LS-102

LS-102 is a selective synoviolin inhibitor (Syvn1). LS-102 inhibits the autoubiquitination of synoviolin with an IC50 of ~15 μM. LS-102 has the potential for rheumatoid arthritis treatment[1][2].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

LS-102 inhibits proliferation of RSCs with an IC50 of 5.4 µM[1]. LS-102 suppresses proliferation of rheumatoid synovial cells (RSCs) in a Syvn1-dependent manner. LS-102 suppresses polyubiquitination of target proteins of Syvn1, including nuclear factor erythroid 2-related factor 2 (NRF2), V247M α-sarcoglycan mutant, and PGC-1β. LS-102 inhibits E3 ligase activity of Synoviolin (Syvn1)[2]. Cell Viability Assay[1] Cell Line: Rheumatoid synovial cells (RSCs) Concentration: 20, 40, 60 μM Incubation Time: 12 hours Result: Inhibited proliferation of RSCs with an IC50 of 5.4 µM.

LS-102 (1.3-4 mg/kg; i.p.; daily for 4 weeks) reduces clinical severity scores in a CIA model[1]. Animal Model: 7-week-old DBA/1 male mice (CIA model)[1] Dosage: 1.3, 4.0 mg/kg Administration: I.p.; daily for 4 weeks Result: Reduced the clinical severity scores.

[1]. Fujita H, et al. Identification of the inhibitory activity of walnut extract on the E3 ligase Syvn1. Mol Med Rep. 2018 Dec;18(6):5701-5708.

[2]. Yagishita N, et al. RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of rheumatoidarthritis. Int J Mol Med. 2012 Dec;30(6):1281-6.