NSC-687852

• CAT Number: I000111
• CAS Number: 1009817-63-3
• Molecular Formula: C₂₂H₁₇N₃O₆
• Molecular Weight: 419.39
• Purity: ≥95%
• Target: Apoptosis Inducers
• Solubility: DMSO: ≥ 44 mg/mL
• Storage: Store at 4°C
• InChI: InChI=1S/C22H17N3O6/c1-2-21(26)23-13-17(11-15-3-7-19(8-4-15)24(28)29)22(27)18(14-23)12-16-5-9-20(10-6-16)25(30)31/h2-12H,1,13-14H2/b17-11+,18-12+
• InChIKey: GFARQYQBWJLZMW-JYFOCSDGSA-N
• SMILES: C=CC(=O)N1CC(=CC2=CC=C(C=C2)[N+](=O)[O])C(=O)C(=CC3=CC=C(C=C3)[N+](=O)[O-])C1

NSC-687852 (CAT: I000111), also known as b-AP15, is a specific inhibitor of the deubiquitinating enzymes UCHL5 and Usp14 within the 26S proteasome. It effectively blocks the deubiquitinating activity of the 26S proteasome and inhibits the function of two regulatory-particle-associated deubiquitinases, UCHL5 and USP14, resulting in the accumulation of polyubiquitin. b-AP15 induces tumor cell apoptosis independent of TP53 status and overexpression of the apoptosis inhibitor BCL2. In multiple myeloma cell lines and solid tumor models, b-AP15 demonstrates caspase-dependent and caspase-independent apoptotic effects. Additionally, b-AP15 has shown inhibitory activity against the selenoprotein thioredoxin reductase (TrxR). In various in vivo models, b-AP15 exhibits tumor growth inhibition, organ infiltration suppression, and prolonged survival. Combination therapies involving b-AP15 have demonstrated synergistic anti-multiple myeloma activity.

Reference

1:Synthesis and evaluation of derivatives of the proteasome deubiquitinase inhibitor b-AP15. Wang X, D/’Arcy P, Caulfield TR, Paulus A, Chitta K, Mohanty C, Gullbo J, Chanan-Khan A, Linder S.Chem Biol Drug Des. 2015 Nov;86(5):1036-48. doi: 10.1111/cbdd.12571. Epub 2015 May 27. PMID: 25854145 Free PMC Article2:Inhibitory effect of b-AP15 on the 20S proteasome. Huang L, Jung K, Chen CH.Biomolecules. 2014 Oct 14;4(4):931-9. doi: 10.3390/biom4040931. PMID: 25317846 Free PMC Article3:The 19S Deubiquitinase inhibitor b-AP15 is enriched in cells and elicits rapid commitment to cell death. Wang X, Stafford W, Mazurkiewicz M, Fryknäs M, Brjnic S, Zhang X, Gullbo J, Larsson R, Arnér ES, D/’Arcy P, Linder S.Mol Pharmacol. 2014 Jun;85(6):932-45. doi: 10.1124/mol.113.091322. Epub 2014 Apr 8. PMID: 24714215 Free Article4:Proapoptotic effects of the novel proteasome inhibitor b-AP15 on multiple myeloma cells and natural killer cells. Feng X, Holmlund T, Zheng C, Fadeel B.Exp Hematol. 2014 Mar;42(3):172-82. doi: 10.1016/j.exphem.2013.11.010. Epub 2013 Nov 27. PMID: 24291587