935888-16-7

Upstream product

• 1010136-50-1 tert-butyl [(1S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]carbamate 
• 1609959-46-7 C₁₇H₂₅NO₄ 
• 265996-13-2 (3RS,4S)-4-N-(tert-butyloxycarbonyl)amino-3-hydroxy-2-methyl-5-phenylpent-1-ene 
• 87694-53-9 Boc-Phe-OH N,O-dimethyl hydroxamate 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 935888-15-6 benzyl (S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-ylcarbamate 

Downstream Products

• 960374-64-5 C₂₉H₃₇N₃O₆ 
• 1620107-59-6 C₂₈H₃₇F₂N₇O₆ 
• 935888-69-0 N-[(2S)-3-methoxy-1-[[(2S)-3-methoxy-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide 

Relevant academic research and scientific papers

LMP2 Inhibitors as a Potential Treatment for Alzheimer's Disease

The immunoproteasome (iP), an inducible proteasome variant harboring three immunosubunits, low molecular mass polypeptide-2 (LMP2), multicatalytic endopeptidase complex subunit-1, and low molecular mass polypeptide-7 (LMP7), is involved in multiple facets of inflammatory responses. We recently reported that YU102, a dual inhibitor of the iP subunit LMP2 and the constitutive proteasome catalytic subunit β1, ameliorates cognitive impairments in mouse models of Alzheimer's disease (AD) independently of amyloid deposits. To investigate whether inhibition of LMP2 is sufficient to improve the cognitive functions of AD mice, here we prepared 37 YU102 analogues and identified a potent LMP2 inhibitor DB-310 (28) (IC50: 80.6 nM) with improved selectivity and permeability in cells overexpressing ABCB1 transporters. We show that DB-310 induces suppression of IL-1α production in microglia cells and improves cognitive functions in the Tg2576 transgenic mouse model of AD. This study supports that inhibition of LMP2 is a promising therapeutic strategy for treatment of AD.

Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from β-amino acid as proteasome inhibitors

A series of novel tripeptidyl epoxyketone derivatives constructed from β-amino acid were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were tested for their proteasome inhibitory activities and selected compounds were tested for their anti-proliferation activities against two multiple myeloma (MM) cell lines RPMI 8226 and NCI-H929. Among them, eleven compounds exhibited proteasome inhibitory rates of more than 50% at the concentration of 1 μg/mL and nine compounds showed anti-proliferation activities with IC50 values at low micromolar level. Compound 20h displayed the most potent proteasome inhibitory activities (IC50: 0.11 ± 0.01 μM) and anti-proliferation activities with IC50 values at 0.23 ± 0.01 and 0.17 ± 0.02 μM against two tested cell lines. Additionally, the poly-ubiquitin accumulation in the western blot analysis supported that proteasome inhibition in a cellular system was induced by compound 20h. All these experimental results confirmed that β-amino acid can be introduced as a building block for the development of proteasome inhibitors.

Compounds for enzyme inhibition

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administer