TBAJ-876   Click here for help

GtoPdb Ligand ID: 13132

Synonyms: compound 46 [PMID: 30803745]
PDB Ligand
Compound class: Synthetic organic
Comment: TBAJ-876, an analogue of bedaquiline, was discovered at the University of Auckland following a lead optimization project to identify novel members of the diarylquinolines class of antibacterial compounds [3]. TBAJ-876 has a more favourable ADME profile, lower risk of QT prolongation, and more potent antimycobacterial activity than bedaquiline [3].
See also our entry for TBAJ-587 that was identified in the same study.
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 11
Hydrogen bond donors 1
Rotatable bonds 13
Topological polar surface area 115.93
Molecular weight 657.55
XLogP 0.94
No. Lipinski's rules broken 3

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 CN(C)CC[C@@](C1=CC(=NC(=C1)OC)OC)([C@H](C2=C(C(=NC(=C2)OC)OC)OC)C3=C(N=C4C=CC(=CC4=C3)Br)OC)O
Isomeric SMILES CN(C)CC[C@@](C1=CC(=NC(=C1)OC)OC)([C@H](C2=CC(=NC(=C2OC)OC)OC)C3=C(N=C4C=CC(=CC4=C3)Br)OC)O
InChI InChI=1S/C31H37BrN4O7/c1-36(2)12-11-31(37,19-15-24(38-3)34-25(16-19)39-4)27(21-17-26(40-5)35-30(43-8)28(21)41-6)22-14-18-13-20(32)9-10-23(18)33-29(22)42-7/h9-10,13-17,27,37H,11-12H2,1-8H3/t27-,31-/m1/s1
InChI Key HHDDKDPLFXIPBX-DLFZDVPBSA-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
TBAJ-876 is under clinical development as an oral treatment for TB. Phase 1 studies, to evaluate safety, tolerability, and pharmacokinetics in healthy adults (NCT04493671, NCT05526911) have been completed. A Phase 2 trial to evaluate the safety and efficacy of TBAJ-876 in combination with pretomanid and linezolid in adult participants with drug-susceptible tuberculosis (DS-TB) is due to commence in 2024.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Functionally, TBAJ-876 inhibits mycobacterial ATP synthase [1].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04493671 Evaluate Safety, Tolerability, PK of TBAJ-876 in Healthy Adults Phase 1 Interventional Global Alliance for TB Drug Development
NCT05526911 A Phase 1, Drug-Drug Interaction Study of TBAJ-876 in Healthy Adults Phase 1 Interventional Global Alliance for TB Drug Development
NCT06058299 Phase 2 Trial Assessing TBAJ876 or Bedaquiline, With Pretomanid and Linezolid in Adults With Drug-sensitive Pulmonary Tuberculosis Phase 2 Interventional Global Alliance for TB Drug Development