ACHN-975   Click here for help

GtoPdb Ligand ID: 13333

PDB Ligand
Compound class: Synthetic organic
Comment: ACHN-975 is a hydroxamate-based inhibitor of bacterial UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) and first-in-class to advance to clinical evaluation [2].
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 5
Rotatable bonds 7
Topological polar surface area 124.68
Molecular weight 369.42
XLogP 0.54
No. Lipinski's rules broken 0

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 CC(C)([C@@H](C(=O)NO)NC(=O)C1=CC=C(C#CC#C[C@@H]2C[C@H]2CO)C=C1)N
Isomeric SMILES CC(C)([C@@H](C(=O)NO)NC(=O)C1=CC=C(C=C1)C#CC#C[C@@H]2C[C@H]2CO)N
InChI InChI=1S/C20H23N3O4/c1-20(2,21)17(19(26)23-27)22-18(25)14-9-7-13(8-10-14)5-3-4-6-15-11-16(15)12-24/h7-10,15-17,24,27H,11-12,21H2,1-2H3,(H,22,25)(H,23,26)/t15-,16+,17-/m1/s1
InChI Key GOCUUDXEOKIQRU-IXDOHACOSA-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
ACHN-975 (formulated for intravenous administration) progressed to Phase 1 clinical evaluation, but development was halted due to cardiotoxicity concerns [2].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The antibacterial MMOA is inhibition of LpxC [2], which is an essential enzyme in the biosynthesis of lipid A (also know as endotoxin), the hydrophobic anchor of lipopolysaccharide (LPS) and a major component of the outer membrane of Gram-negative bacteria [4-5]. LpxC is an attractive target for the development of antibacterial agents against Gram-negative bacterial pathogens, although safety and activity issues have so far precluded approval for clinical use of these drugs [1,3].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01597947 A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ACHN-975 in Healthy Volunteers Phase 1 Interventional Achaogen, Inc.
NCT01870245 A Multiple Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of ACHN-975 in Healthy Volunteers Phase 1 Interventional Achaogen, Inc.