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Series GSE144326 Query DataSets for GSE144326
Status Public on Jan 31, 2021
Title Selective inhibition of the second bromodomain of BET family proteins results in robust antitumor activity in preclinical models of acute myeloid leukemia
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Dual bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4 and BRDt only displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of GI toxicity, have presented as dose limiting adverse events that may prevented escalation to higher dose levels for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain (BD2) of the four BET family proteins. In contrast to the broad antiproliferative activities observed with DbBi, ABBV-744 displayed significant antiproliferative activities largely but not exclusively in cancer cell lines derived from AML and androgen receptor (AR) positive prostate cancer. Studies in AML xenograft models demonstrated anti-tumor efficacy for ABBV-744 that was comparable to the pan-BET inhibitor ABBV-075 but with improved tolerability. Enhanced anti-tumor efficacy was also observed with the combination of ABBV-744 and the Bcl-2 inhibitor, venetoclax (ABT-199) compared to monotherapies of either agent alone. These results collectively support the clinical evaluation of ABBV-744 in AML (Clinical identifier: NCT03360006).
Overall design mRNA profiles of AML and NSCLC cell lines treated with ABBV-075, ABBV-744 or DMSO control, for 24 hours, using Illumina HiSeq3000.
Contributor(s) Lu X, Zhang L, Cai T, Lin X
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Submission date Jan 27, 2020
Last update date Jan 31, 2021
Contact name Xin Lu
Phone 847-937-7942
Organization name Abbvie
Department Oncology Discovery
Street address 1 North Waukegan Rd
City North Chicago
State/province IL
ZIP/Postal code 60064
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (24)
GSM4285903 GTG_140_07: SKM-1
GSM4285904 GTG_140_08: SKM-1
GSM4285905 GTG_140_09: SKM-1
BioProject PRJNA603369
SRA SRP245430

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE144326_AMLCellLine.BETi_Treatment.RNASeq.FPKM.txt.gz 1.6 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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