Orally active immune modulator that suppresses inflammatory cytokines production and blocks P-glycoprotein-mediated MDR in vitro and in vivo.
Y-320 is an orally active immune modulator that inhibits IL-15-stimulated (100 ng/mL) IL-17 production from T-cells (IC50 = 57.4 nM using human CD4 T-cells & hIL-15; IC50 = 25.7/52.4 nM using murine CD4/Th17 T-cells and mIL-15 plus 1 μ/mL mCXCL12 & 1 μg/mL anti-CD3ε mAb) and prevents type II collagen-induced arthritis (CIA) in mice in vivo (0.3 to 3 mg/kg via daily p.o.). Y-320 is a P-glycoprotein (P-gp) substrate and sensitizes MDR tumor cells to chemotherapy drugs in cultures (paclitaxel IC50 with/without 500 nM Y-320 = 0.21/1.15 μM/Bads-200, 16/153 nM/Bads-72 breast cancer cells) and in mice in vivo (0% vs. 78% tumor growth suppression by 15 mg/kg PTX without or with 15 mg/kg Y-320 i.v.).
Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320
Premature termination codons (PTC) cause over 10% of genetic disease cases. Some aminoglycosides that bind to the ribosome decoding center can induce PTC readthrough and restore low levels of full-length functional proteins. However, concomitant inhibition of protein synthesis limits the
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