2022
DOI: 10.1038/s41598-022-25587-3
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Impact of SNPs, off-targets, and passive permeability on efficacy of BCL6 degrading drugs assigned by virtual screening and 3D-QSAR approach

Abstract: B-cell lymphoma 6 (BCL6) regulates various genes and is reported to be overexpressed in lymphomas and other malignancies. Thus, BCL6 inhibition or its tagging for degradation would be an amenable therapeutic approach. A library of 2500 approved drugs was employed to find BCL6 inhibitory molecules via virtual screening. Moreover, the 3D core structure of 170 BCL6 inhibitors was used to build a 3D QSAR model and predict the biological activity. The SNP database was analyzed to study the impact on the destabiliza… Show more

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Cited by 2 publications
(4 citation statements)
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“…Accumulation of data from numerous studies has demonstrated the contribution of various missense SNPs to the progression of diverse diseases 36 , 37 , 40 . However, there is a paucity of knowledge regarding the alterations in OX1R structural and conformational dynamics caused by detrimental missense SNPs.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Accumulation of data from numerous studies has demonstrated the contribution of various missense SNPs to the progression of diverse diseases 36 , 37 , 40 . However, there is a paucity of knowledge regarding the alterations in OX1R structural and conformational dynamics caused by detrimental missense SNPs.…”
Section: Discussionmentioning
confidence: 99%
“…Single nucleotide polymorphisms (SNPs) represent a prevalent and stable type of genetic variation within the human genome. They not only serve as valuable biological markers but can also be linked to the development of complex diseases, abnormalities, and variations in drug responses 36 40 . Nonsynonymous SNPs (nsSNPs) in protein-coding regions, which result in alterations to amino acid sequences and the potential creation of mutated proteins with new structural and functional properties, have garnered significant interest.…”
Section: Introductionmentioning
confidence: 99%
“…13 Moreover, its interactions with various molecules, especially drugs, can significantly alter membrane characteristics, potentially affecting drug permeability and efficacy. 14 Recent studies have also emphasized the potential of DPPC in understanding the toxicological effects of nanoparticles on model membranes and lung surfactants, 15 as well as its interaction with glycerol, which can influence the bioavailability of inhaled steroids. 11 Phosphatidylserine (PS) is a lipid that has garnered significant attention due to its unique molecular-scale organization in membranes, especially when cholesterol is present.…”
Section: ■ Introductionmentioning
confidence: 99%
“…DPPC is also a primary constituent of the lung surfactant, a substance that reduces surface tension in the alveoli of the lungs, preventing their collapse during exhalation. , This saturated phospholipid DPPC is known for its ability to exhibit phase coexistence, transitioning between gel and liquid-crystalline states . Moreover, its interactions with various molecules, especially drugs, can significantly alter membrane characteristics, potentially affecting drug permeability and efficacy . Recent studies have also emphasized the potential of DPPC in understanding the toxicological effects of nanoparticles on model membranes and lung surfactants, as well as its interaction with glycerol, which can influence the bioavailability of inhaled steroids .…”
Section: Introductionmentioning
confidence: 99%