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International Journal of Toxicology

International Journal of Toxicology

IF: 1.2
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High-Throughput Drug Screen for Potential Combinations With Venetoclax Guides the Treatment of Transformed Follicular Lymphoma

Published:1 September 2023 DOI: 10.1177/10915818231178693 PMID: 37271574
Zhifeng Li,?Guangchao Pan,?Mengya Zhong,?Li Zhang,?Xingxing Yu,?Jie Zha,?Bing Xu

Abstract

Transformed follicular lymphoma (t-FL) is an aggressive malignancy that is refractory and rapidly progressing with poor prognosis. There is currently no effective treatment. High-throughput screening (HTS) platforms are used to profile the sensitivity or toxicity of hundreds of drug molecules, and this approach is applied to identify potential effective treatments for t-FL. We randomly selected a compound panel from the School of Pharmaceutical Sciences Xiamen University, tested the effects of the panel on the activity of t-FL cell lines using HTS and the CCK-8 assay, and identified compounds showing synergistic anti-proliferative activity with the Bcl-2 inhibitor venetoclax (ABT-199). Bioinformatics tools were used to analyze the potential synergistic mechanisms. The single-concentration compound library demonstrated varying degrees of activity across the t-FL cell lines evaluated, of which the Karpas422 cells were the most sensitive, but it was the cell line with the least synergy with ABT-199. We computationally identified 30 drugs with synergistic effects in all cell lines. Molecularly, we found that the targets of these 30 drugs didn't directly regulate Bcl-2 and identified 13 medications with high evidence value above .9 of coordination with ABT-199, further confirming TP53 may play the largest role in the synergistic effect. Collectively, these findings identified the combined regimens of ABT-199 and further suggested that the mechanism is far from directly targeting Bcl-2, but rather through the regulation and synergistic action of p53 and Bcl-2. This study intended to reveal the best synergistic scheme of ABT-199 through HTS to more quickly inform the treatment of t-FL.

Substances (13)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
ABT-199 1257044-40-8 C45H50ClN7O7S - Inquiry
ABT-199 1257044-40-8 C45H50ClN7O7S - Inquiry
ABT-199 1257044-40-8 - Inquiry
ABT-199 1257044-40-8 - Inquiry
ABT199 1257044-40-8 - Inquiry
ABT199 1257044-40-8 - Inquiry

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