化学性质：                                                                                                             

产品描述：                                                                                                            

VLX1570, an analogue of b-AP15, is a competitive inhibitor of deubiquitinase activity, with an IC50 of appr 10 uM.

VLX1570 inhibits USP14 and UCHL5 activity of 19S regulatory particles, and the inhibition of USP14 is more pronounced. VLX1570 (1 uM) shows inhibitory activity against USP14 in KMS-11 myeloma cells. VLX1570 exhibits an IC50 of 0.58 uM on HCT116 cells[1]. VLX1570 binds to recombinant USP14 with Kd of 1.5-18 uM using two different sources of recombinant protein, and the Kd for recombinant UCHL5 is higher (14-18 uM) compared to that of USP14. VLX1570 has potent antiproliferative activities on multiple myeloma cells, with IC50s of 43 ± 2 nM, 74 ± 2 nM, 126 ± 3 nM, and 191 ± 1 nM for KMS-11, RPMI8226, OPM-2, and OPM-2-BZR cells, respectively[2]. VLX1570 suppresses the viability of BCWM.1 cells, with an EC50 of 20.22 nM. VLX1570 (100, 250, 500 nM) induces significant apoptosis by 12 h in a dose-dependent manner in all Waldenstrom macroglobulinemia (WM) cell lines tested, including BCWM.1/IR (IR) and BCWM.1/BR (BR) subclones. VLX1570 (100, 250, 500 nM) also causes ER stress machinery and mitochondrial damage in WM cells. VLX1570 (250 nM) downregulates BCR-signalosome components and their end effectors, as well as CXCR4 expression in WM cells[3].

VLX1570 (3 mg/kg) significantly decreases tumor growth in mice bearing KMS-11 multiple myeloma cells[2]. VLX1570 (4.4 mg/kg, i.p.) markedly suppresses tumor growth, without obvious weight loss and other signs of systemic toxicity in the Waldenstrom macroglobulinemia (WM)-bearing mice[3].

特别提醒：