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Homo sapiens

ABSTRACT: Gene expression profile of multiple myeloma cell lines treated with CB-5083

PROVIDER: PRJNA395929 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5871840_1.fastq.gz	Fastqsanger.gz
	SRR5871840_2.fastq.gz	Fastqsanger.gz
	SRR5871850_1.fastq.gz	Fastqsanger.gz
	SRR5871850_2.fastq.gz	Fastqsanger.gz
	SRR5871841_1.fastq.gz	Fastqsanger.gz

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Homo sapiens

Project description:Gene expression analysis of multiple myeloma cell lines treated with novel PIM2 inhibitor JP11646

| PRJNA353370 | ENA

Gene expression profile of multiple myeloma cell lines treated with CB-5083

Project description:The goal was to determine the gene expression differences between CB-5083 and Bortezomib treated multiple myeloma cell lines Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system (UPS) and CB-5083, a first in class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematological and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma (MM) cell lines and a number of in vivo MM models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response (UPR) and apoptosis. CB-5083 decreases viability in MM cell lines and patient derived MM cells, including those with background proteasome inhibitor (PI) resistance. CB-5083 has a unique mechanism of action that combines well with PIs which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI. In vivo studies using clinically relevant MM models demonstrate that single-agent CB-5083 inhibits tumor growth and combines well with MM standard of care agents. Our preclinical data demonstrate the efficacy of CB-5083 in several MM disease models and provide the rationale for clinical evaluation as monotherapy and in combination in MM.

2017-10-26 | GSE101923 | GEO

Homo sapiens

Project description:Small-molecule inhibitor JQ1 effect on multiple myeloma cell lines

| PRJNA145885 | ENA