Gutenberg Open Science: Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-5807

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DC Field	Value	Language
dc.contributor.author	Saeed, Mohamed E. M.	-
dc.contributor.author	Kadioglu, Onat	-
dc.contributor.author	Greten, Henry Johannes	-
dc.contributor.author	Yildirim, Adem	-
dc.contributor.author	Mayr, Katharina	-
dc.contributor.author	Wenz, Frederik	-
dc.contributor.author	Giordano, Frank	-
dc.contributor.author	Efferth, Thomas	-
dc.date.accessioned	2021-05-10T09:44:45Z	-
dc.date.available	2021-05-10T09:44:45Z	-
dc.date.issued	2021	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/5816	-
dc.description.abstract	BACKGROUND 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. METHODS The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical 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. RESULTS 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. CONCLUSIONS In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-5807	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 09 Chemie, Pharmazie u. Geowissensch.	de
jgu.organisation.number	7950	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Investigational new drugs	de
jgu.journal.volume	39	de
jgu.pages.start	670	de
jgu.pages.end	685	de
jgu.publisher.year	2021	-
jgu.publisher.name	Springer Science + Business Media B.V.	de
jgu.publisher.place	Dordrecht u.a.	de
jgu.publisher.uri	https://doi.org/10.1007/s10637-020-01037-7	de
jgu.publisher.issn	1573-0646	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	570	de
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1007/s10637-020-01037-7
jgu.organisation.ror	https://ror.org/023b0x485
Appears in collections:	JGU-Publikationen

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