(+)-JQ1   Click here for help

GtoPdb Ligand ID: 7511

Compound class: Synthetic organic
Comment: JQ1 is a selective and potent inhibitor of BET family bromodomains [2]. This is a compound from the Structural Genomics Consortium's (SGC) Epigenetics Probes Collection.
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Ligand Activity Visualisation Charts

These 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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View interactive charts of activity data across species

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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 CDK toolkit. 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 5
Hydrogen bond donors 0
Rotatable bonds 5
Topological polar surface area 97.09
Molecular weight 456.14
XLogP 6.41
No. Lipinski's rules broken 1
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.

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Canonical SMILES O=C(OC(C)(C)C)CC1N=C(c2ccc(cc2)Cl)c2c(n3c1nnc3C)sc(c2C)C
Isomeric SMILES O=C(OC(C)(C)C)C[C@@H]1N=C(c2ccc(cc2)Cl)c2c(n3c1nnc3C)sc(c2C)C
InChI InChI=1S/C23H25ClN4O2S/c1-12-13(2)31-22-19(12)20(15-7-9-16(24)10-8-15)25-17(11-18(29)30-23(4,5)6)21-27-26-14(3)28(21)22/h7-10,17H,11H2,1-6H3/t17-/m0/s1
InChI Key DNVXATUJJDPFDM-KRWDZBQOSA-N
Bioactivity Comments
JQ1 displaces BRD4 from nuclear chromatin in vitro, induces squamous cell differentiation and growth arrest in NUT midline carcinoma (NMC) cells and exhibits antitumour activity in xenograft models of NMC [2]. (+)-JQ1 binds to BRD4-BD1 with a Kd of approximately 50nM and to BRD4-BD2 with a Kd of 90 nM [2]. In male mice, (+)-JQ1 inhibits the chromatin remodelling that is essential during spermatogenesis, and has a complete and reversible contraceptive effect [3]. Crystallographic study shows that (+)-JQ1 occupies the acetylysine binding site on BRDT, thus preventing BRDT-histone H4 interaction [3].

JQ1-induced inhibition of BET domain containing proteins such as BRD4, inactivates Myc oncogene activity, which in turn switches off expression of programmed death-ligand 1 (PD-L1) and CD47 [1]. Both PD-L1 and CD47 are up-regulated in tumours under Myc control and act in concert to suppress immune detection of the cancer cells. Thus, Myc inhibition appears as a novel immuno-oncology target.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
bromodomain containing 4 Hs Inhibitor Inhibition 7.3 pKd - 2
⤷ pKd 7.3 (Kd 5x10-8 M) [2]
Description: Displacement binding constant to recombinant BRD4-BD1 protein.
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
bromodomain testis associated Mm Inhibitor Inhibition 8.0 pIC50 - 3
⤷ pIC50 8.0 (IC50 1x10-8 M) [3]
Description: Inhibition of H4Kac4 binding to mBRDT-BD1
bromodomain testis associated Hs Inhibitor Inhibition 8.0 pIC50 - 3
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [3]
Description: Inhibition of H4Kac4 binding to hBRDT-BD1