The chromatin accessibility dynamics during cell fate specifications in zebrafish early embryogenesis

Xu, Qiushi; Zhang, Yunlong; Xu, Wei; Liu, Dong; Jin, Wenfei; Chen, Xi; Hong, Ni

doi:10.1101/2023.10.13.562312

Cited by 1 publication

(1 citation statement)

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“…AV25R might inhibit signaling pathways by binding to GSTP1, which, in turn, regulate its expression [54]. The downregulation might also be part of a feedback mechanism where GSTP1 protein, or its downstream signaling components, regulate the expression of their own gene in response to substance binding [55].…”

Section: Discussionmentioning

confidence: 99%

Exploring Thiazolopyridine AV25R: Unraveling of Biological Activities, Selective Anti-Cancer Properties and In Silico Target and Binding Prediction in Hematological Neoplasms

Ladwig,

Gupta,

Ehlers

et al. 2023

Molecules

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Thiazolopyridines are a highly relevant class of small molecules, which have previously shown a wide range of biological activities. Besides their anti-tubercular, anti-microbial and anti-viral activities, they also show anti-cancerogenic properties, and play a role as inhibitors of cancer-related proteins. Herein, the biological effects of the thiazolopyridine AV25R, a novel small molecule with unknown biological effects, were characterized. Screening of a set of lymphoma (SUP-T1, SU-DHL-4) and B- acute leukemia cell lines (RS4;11, SEM) revealed highly selective effects of AV25R. The selective anti-proliferative and metabolism-modulating effects were observed in vitro for the B-ALL cell line RS4;11. Further, we were able to detect severe morphological changes and the induction of apoptosis. Gene expression analysis identified a large number of differentially expressed genes after AV25R exposure and significant differentially regulated cancer-related signaling pathways, such as VEGFA-VEGFR2 signaling and the EGF/EGFR pathway. Structure-based pharmacophore screening approaches using in silico modeling identified potential biological AV25R targets. Our results indicate that AV25R binds with several proteins known to regulate cell proliferation and tumor progression, such as FECH, MAP11, EGFR, TGFBR1 and MDM2. The molecular docking analyses indicates that AV25R has a higher binding affinity compared to many of the experimentally validated small molecule inhibitors of these targets. Thus, here we present in vitro and in silico analyses which characterize, for the first time, the molecular acting mechanism of AV25R, including cellular and molecular biologic effects. Additionally, this predicted the target binding of the molecule, revealing a high affinity to cancer-related proteins and, thus, classified AVR25 for targeted intervention approaches.

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Section: Discussionmentioning

confidence: 99%