Synonyms: ABBV 744 | ABBV744
Compound class:
Synthetic organic
Comment: ABBV-744 is an investigational, orally bioavailable BET family protein (BRD) inhibitor, that was developed for antiproliferative potential in cancer [1]. It was designed to selectively target the BD2 domain of BET family proteins, in an effort to limit potential on-target adverse activity associated with BD1 interactions. In vivo, ABBV-744 produced fewer platelet and gastrointestinal toxicities than a dual BD1/2-targeting compound in preclinical models. Its antiproliferative effects are primarily evident in acute myeloid leukaemia cell lines and in prostate cancer cells that express the full-length androgen receptor (AR).
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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Bioactivity Comments |
ABBV-744 exhibits robust antiproliferative activity in prostate cancer xenografts [1]. At the molecular level it displaces BRD4 from androgen receptor (AR)-containing super-enhancers and inhibits AR-dependent transcription. Like the AR antagonist enzalutamide, ABBV-744 induces cell cycle arrest in G1 and then senescence in LNCaP cells. No also significant activity of ABBV-744 was detected in a screening panel of 75 kinases and 22 diverse bromodomain-containing proteins. |