birabresib   Click here for help

GtoPdb Ligand ID: 8359

Synonyms: MK-8628 | OTX-015 | OTX015
PDB Ligand
Compound class: Synthetic organic
Comment: OTX015 inhibits interaction between bromodomain and extra-terminal (BET) family of bromodomain-containing proteins (BRDs) BET domains and acetylated histone 4 (AcH4). It is an orally available novel BRD2/3/4 inhibitor with potent preclinical anti-tumour activity [1,4,6,10,12-13]. OTX015 is an analogue of (+)-JQ1.

birabresib 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 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 120.12
Molecular weight 491.12
XLogP 5.74
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 O=C(CC1N=C(c2ccc(cc2)Cl)c2c(n3c1nnc3C)sc(c2C)C)Nc1ccc(cc1)O
Isomeric SMILES O=C(C[C@@H]1N=C(c2ccc(cc2)Cl)c2c(n3c1nnc3C)sc(c2C)C)Nc1ccc(cc1)O
InChI InChI=1S/C25H22ClN5O2S/c1-13-14(2)34-25-22(13)23(16-4-6-17(26)7-5-16)28-20(24-30-29-15(3)31(24)25)12-21(33)27-18-8-10-19(32)11-9-18/h4-11,20,32H,12H2,1-3H3,(H,27,33)/t20-/m0/s1
InChI Key GNMUEVRJHCWKTO-FQEVSTJZSA-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/)
No information available.
Summary of Clinical Use Click here for help
OTX015 is being used in clinical trials to evaluate the compound's effectiveness against solid tumours and haematological malignancies. Click here to link to ClinicalTrials.gov's complete list of OTX015 trials.
Results from Phase 1 trial in patients with hematological malignancies (NCT01713582) are reported in [2], and pharmacokinetic and dose-escalation results from the same study in [9].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The BRDs are important epigenetic regulators of proliferation and differentiation, acting as epigenetic readers. Small molecule BRD inhibitors are being pursued by the pharmaceutical industry as anti-cancer chemotherapeutics [5].[7,11].