LY 3000328

• CAT Number: I001435
• CAS Number: 1373215-15-6
• Molecular Formula: C25H29FN4O5
• Molecular Weight: 484.52
• Purity: 98%
• Synonyms: [(3R,4S)-4-[(4-fluorobenzoyl)amino]-6-[4-(oxetan-3-yl)piperazin-1-yl]-3,4-dihydro-2H-chromen-3-yl] N-methylcarbamate;LY 3000328;LY3000328;Z-FL-COCHO
• Target: Cathepsin
• Solubility: DMSO > 75 mg/ml
• Appearance: Solid powder
• Storage: Store at -20°C
• IUPAC Name: [(3R,4S)-4-[(4-fluorobenzoyl)amino]-6-[4-(oxetan-3-yl)piperazin-1-yl]-3,4-dihydro-2H-chromen-3-yl] N-methylcarbamate
• InChI: InChI=1S/C25H29FN4O5/c1-27-25(32)35-22-15-34-21-7-6-18(29-8-10-30(11-9-29)19-13-33-14-19)12-20(21)23(22)28-24(31)16-2-4-17(26)5-3-16/h2-7,12,19,22-23H,8-11,13-15H2,1H3,(H,27,32)(H,28,31)/t22-,23-/m0/s1
• InChIKey: NDEBZCZEAVMSQF-GOTSBHOMSA-N
• SMILES: CNC(=O)OC1COC2=C(C1NC(=O)C3=CC=C(C=C3)F)C=C(C=C2)N4CCN(CC4)C5COC5

LY 3000328(CAT: I001435) is a novel inhibitor of Cathepsin S, an enzyme involved in antigen processing and presentation. It is predominantly expressed in antigen-presenting cells and plays a role in invariant chain processing and MHCII antigen presentation, which leads to CD4+ T-cell activation. By inhibiting Cathepsin S, LY 3000328 blocks MHCII antigen presentation, potentially resulting in a T-cell-selective immunosuppressant agent. This could offer an improved safety profile compared to existing treatments for autoimmune-based inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis.

Reference

[1]. Lee-Dutra A, Wiener DK, Sun S. Cathepsin S inhibitors: 2004-2010. Expert Opin Ther Pat. 2011 Mar;21(3):311-37. doi: 10.1517/13543776.2011.553800.
[2]. J. M. Wiener, John; Sun, et al. Recent Advances in the Design of Cathepsin S Inhibitors. Current Topics in Medicinal Chemistry, 2010, 10, (7): 717-732(16).
[3]. Link JO, Zipfel S. Advances in cathepsin S inhibitor design. Curr Opin Drug Discov Devel. 2006 Jul;9(4):471-82.