Saeed, Mohamed E. M.; Kadioglu, Onat; Greten, Henry Johannes; Yildirim, Adem; Mayr, Katharina; Wenz, Frederik; Giordano, Frank A.; Efferth, Thomas published the artcile< Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma>, Electric Literature of 1492-18-8, the main research area is aclarubicin idarubicin anticancer agent cytotoxicity BRAF PIK3R1 mutation glioblastoma; Drug repurposing; Precision medicine; Targeted chemotherapy; Virtual drug screening.
Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochem. corroborated RNA-sequencing data. The expression of addnl. markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chem. library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. In conclusion, we identified novel small mols. via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.
Investigational New Drugs published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (ABCA13). 1492-18-8 belongs to class alcohols-buliding-blocks, and the molecular formula is C20H21CaN7O7, Electric Literature of 1492-18-8.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts