sabutoclax (ONT-701)

Herein, a self-delivery biomedicine (designated as BSC) is developed by the self-assembly of Bortezomib (BTZ), Sabutoclax (Sab) and Chlorin e6 (Ce6). Of special note, the coordination-driven self-assembly of BSC is pH-responsive, which could be disassembled for controlled drug release upon tumor acidic microenvironment. This study would expand the applicability of self-delivery nanomedicine with sophisticated mechanisms for tumor treatment.

Moreover, we identified SGPP1, RHOQ, and PDGFRB as potential targets for TP53-mutant COAD, and illuminated that the high-risk patients might benefit from IGFR-3801, Staurosporine, and Sabutoclax...Besides, we identified novel therapeutic targets and potential sensitive agents for TP53-mutant COAD with high risk. Our findings provided not only a new strategy for prognosis management but also new clues for drug application and precision treatment in COAD with TP53 mutations.

We successfully established and verified a novel circadian clock-related gene signature, which could stratify patients with different risk and be reflective of the therapeutic effect of molecular targeted therapy. Our findings could incorporate the pharmacological modulation of circadian clock into future therapeutic strategies.

The SKMM2 MM cell line, harboring t(11;14), del(CYLD) was highly sensitive to Venetoclax...Of note, these latter resulted sensitive to Sabutoclax, a panBCL2-axis inhibitor... Our study showed a link between the genomic archi- tecture and transcriptome in MM, where CNAs and CRs had a stron- ger impact on expression than gene mutations. Within these lattes UPON GENOMIC HS ones need further testing as they may represent future treatment targets. Moreover, the mutational status is crucial since, due to the transcriptomic consequences of bi-allelic events which provides bio- logical basis for the observed prognostic impact of “double-hit” MM.

The SKMM2 MM cell line, harboring t(11;14), del(CYLD) e NOXAamp was highly sensitive to Venetoclax...Of note, these latter resulted sensitive to the pan-BCL2 axis inhibitor Sabutoclax...Moreover, the mutational status is crucial since, while mono-allelic events are often of little transcriptional value, compound heterozygosity carries a huge influence on transcriptomic which provides biological basis for the observed prognostic impact of “double-hit” MM. Finally, we suggest that a comprehensive profiling of the BCL2 pathway may identify biomarkers of sensitivity to BCL2 inhibitors in addition to the t(11;14).