20S Proteasome activator 1

• CAT Number: I043334
• CAS Number: 2761578-18-9
• Molecular Formula: C27H19ClF2N2OS
• Molecular Weight: 492.97
• Purity: ≥95%
• Synonyms: 3-(2-chlorophenothiazin-10-yl)-N,N-bis(4-fluorophenyl)propanamide
• InChI: InChI=1S/C27H19ClF2N2OS/c28-18-5-14-26-24(17-18)31(23-3-1-2-4-25(23)34-26)16-15-27(33)32(21-10-6-19(29)7-11-21)22-12-8-20(30)9-13-22/h1-14,17H,15-16H2
• InChIKey: ZFFNQHQEQWDWBM-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)N(C3=C(S2)C=CC(=C3)Cl)CCC(=O)N(C4=CC=C(C=C4)F)C5=CC=C(C=C5)F

20S Proteasome activator 1 is a potent 20S proteasome activator with EC200 values of 0.3 μM, 0.7 μM and 1.8 μM for trypsin-like site, chymotrypsin-like site and caspase-like site. 20S Proteasome activator 1 translates well in a cellular system, preventing the accumulation of the pathogenic A53T mutant of α-synuclein. 20S Proteasome activator 1 can be used for researching neurodegenerative diseases[1].
20S Proteasome activator 1 (compound 19) (2.5-15 μM; 45 min) degrades 73% α-synuclein at 10 μM, and over 80% at 15 μM[1].
20S Proteasome activator 1 (5-15 μM; 24 h) reduces 25% A53T mutant, and dose-dependently reduces enhancement of α-synuclein in Hek-293T cells (transiently transfected with an A53T mutant α-synuclein plasmid) at 5 μM; decreases 67% A53T α-synuclein at 15 μM[1].

Reference

[1]. Staerz SD, et al. Design, Synthesis, and Biological Evaluation of Potent 20S Proteasome Activators for the Potential Treatment of α-Synucleinopathies. J Med Chem. 2022 May 12;65(9):6631-6642.
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