ABBV-744   Click here for help

GtoPdb Ligand ID: 10730

Synonyms: ABBV 744 | ABBV744
PDB Ligand
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).

ABBV-744 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 96.35
Molecular weight 491.22
XLogP 5.8
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCNC(=O)c1cc2c([nH]1)c(=O)n(cc2c1cc(ccc1Oc1c(C)cc(cc1C)F)C(O)(C)C)C
Isomeric SMILES CCNC(=O)c1cc2c([nH]1)c(=O)n(cc2c1cc(ccc1Oc1c(C)cc(cc1C)F)C(O)(C)C)C
InChI InChI=1S/C28H30FN3O4/c1-7-30-26(33)22-13-20-21(14-32(6)27(34)24(20)31-22)19-12-17(28(4,5)35)8-9-23(19)36-25-15(2)10-18(29)11-16(25)3/h8-14,31,35H,7H2,1-6H3,(H,30,33)
InChI Key OEDSFMUSNZDJFD-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.