ANXA3 degrader 18a5   Click here for help

GtoPdb Ligand ID: 13778

Synonyms: compound 18a5 [PMID: 40013713]
Compound class: Synthetic organic
Comment: Expression of annexin A3 (ANXA3) protein is elevated in a significant proportion of triple-negative breast cancer (TNBC) clinical samples, and this is associated with poor prognosis. This molecule behaves as a degrader of the ANXA3 protein, thus offering a novel mechanistic approach with therapeutic potential in TNBC [1].
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 8
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 138
Molecular weight 572.75
XLogP 2.32
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 CC(C)N1C2=C(C=CC=C2)C(=NC(C1=O)NC(=S)SCC(=O)N3CCN(CC3)C4=NC=CC=C4)C5=CC=CC=C5
Isomeric SMILES O=C1C(NC(SCC(N2CCN(C3=NC=CC=C3)CC2)=O)=S)N=C(C4=CC=CC=C4)C5=CC=CC=C5N1C(C)C
InChI InChI=1S/C30H32N6O2S2/c1-21(2)36-24-13-7-6-12-23(24)27(22-10-4-3-5-11-22)32-28(29(36)38)33-30(39)40-20-26(37)35-18-16-34(17-19-35)25-14-8-9-15-31-25/h3-15,21,28H,16-20H2,1-2H3,(H,33,39)
InChI Key SXMMTHBOJDWDGR-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
Degrader 18a5 has a DC50 of ~6μM vs. ANXA3 protein. It has anti-tumour activity in a TNBC tumour xenograft model.
Selectivity at ligand targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
annexin A3 Hs None Binding 7.4 pKd - 1
⤷ pKd 7.4 (Kd 4x10-8 M) [1]
Description: Binding affinity for annexin A3, detemined by SPR