Phase 2, multicenter study of the EZH2 inhibitor tazemetostat as monotherapy in adults with relapsed or refractory (R/R) malignant mesothelioma (MM) with BAP1 inactivation. JCO 2018;36:8515–8515. Hassan R, Morrow B, Thomas A, Walsh T, Lee MK, Gulsuner S, et al. Inherited ...
Importantly, depletion ofconfers cellular resistance to bromodomain and extraterminal (BET) protein inhibitor JQ1 and Aurora A kinase inhibitor Alisertib. Furthermore, IHC results of NB tissue array confirmed the positive correlation between BAP1 and MYCN protein. Altogether, our work not only uncovers...
BAP1-IN-1 is an inhibitor of the catalytic activity of BRCA1-associated protein 1 (BAP1), which is related to cancer and can be used to study cancer. 体外活性 在0.1 μM 浓度下经过24小时处理后,BAP1-IN-1 对 BAP1-WT 细胞产生了显著影响,改变了其中的240个基因的表达水平。在 BAP1-KO ...
CDKN2A是细胞周期依赖性激酶抑制基因(cyclin-dependent kinase inhibitor)的简称,也称多重肿瘤抑制基因(multiple tumor suppressor l,MTS1),通过可变剪切可产生不同的转录本,至少编码3个不同的蛋白,其中的两个蛋白分别为p16(INK4)与p14(ARF),p16为细胞周期蛋白依赖的激酶抑制剂,p14可与MDM2结合防止p53被泛素化降解,...
CDKN2A是细胞周期依赖性激酶抑制基因(cyclin-dependent kinase inhibitor)的简称,也称多重肿瘤抑制基因(multiple tumor suppressor l,MTS1),通过可变剪切可产生不同的转录本,至少编码3个不同的蛋白,其中的两个蛋白分别为p16(INK4)与p14(ARF),p16为细胞周期蛋白依赖的激酶抑制剂,p14可与MDM2结合防止p53被泛素化降解,...
Zauderermg, Szlosarek PW, Le Moulec S, et al. EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2022;...
(a) Ub-AMC hydrolysis assay of BAP1 and BAP1/ASXL1DEUin the presence of an H2A peptide that is conjugated to ubiquitin at K119 in a non-hydrolyzable fashion. This conjugate mimics substrates and therefore functions as an inhibitor for Ub-AMC hydrolysis. BAP1 is inhibited more readily by ...
Collectively, these results prove that PT33 is a covalent inhibitor of BAP1. On the basis of these findings, we next examined whether the covalently interaction of BAP1 with PT33 may alter BAP1 sub-cellular location, and found that after IR treatment, PT33 had no apparent effect on the ...
Therefore, MG132 (proteasome inhibitor) was used to test its effect on H2A. It showed that MG132 reversed the reduced-H2A protein expression level induced by BAP1 knockdown (Fig. 5B). To further investigate whether BAP1 deubiquitinated H2A, Co-IP assay was applied. The results showed that ...
reducing BAP1’s catalytic activity has been shown to inhibit leukemia development and extend the survivability of animals [33]. Therefore, in our recent studies, we have identified a first-in-class BAP1 inhibitor by utilizing a high throughput small-molecule screening and tested its activity, ef...