The proposed systems' biomedicine-oriented multi-omics data integration for drug repurposing to provide promising results for the construction of effective clinical therapeutics. To the best of our knowledge, this is the first study reporting epigenome- and transcriptome-based drug repositioning for NF-PitNETs using in silico confirmations.

2 years ago

Journal

YAP1 (Yes associated protein 1) • SOX2 • ZFHX3 (Zinc Finger Homeobox 3) • SOCS1 (Suppressor Of Cytokine Signaling 1) • HMGA2 (High mobility group AT-hook 2) • HBP1 (HMG-Box Transcription Factor 1) • RREB1 (Ras Responsive Element Binding Protein 1)

Mekinist (trametinib) • Ibrance (palbociclib) • linifanib (ABT-869) • Clopixol (zuclopenthixol)

3years

Computational investigation to identify potent inhibitors of the GTPase-Kirsten RAt sarcoma virus (K-Ras) mutants G12C and G12D. (PubMed, Comput Biol Med)

We identified compounds, such as flupentixol, amlodipine, and fluvoxamine, for the G12C mutant and paroxetine, flupentixol, and zuclopenthixol for the G12D mutant with significant inhibitory functions...In contrast, paroxetine and flupentixol to G12D showed a similar trend compared to sotorasib complexes. Thus, despite the very dynamic functionality of K-Ras switches I and II, the binding of shortlisted compounds is highly stable. Therefore, the reported study provides potential drug candidates for K-Ras inhibition that can be further developed with in vitro and in vivo evidence for targeted therapy.

3 years ago

Preclinical • Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12

Lumakras (sotorasib) • Clopixol (zuclopenthixol)