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ErSO-TFPy   Click here for help

GtoPdb Ligand ID: 13693

Synonyms: compound (R)-26 [PMID: 35080871]
Compound class: Synthetic organic
Comment: ErSO-TFPy is a small molecule that exhibits potent cytotoxicity in estrogen receptor alpha (ERα)-positive tumour cells and xenograft models [2]. It is reported to hyperactivate the anticipatory unfolded protein response (a-UPR; a tumour protective mechanism associated with mitogenic steroid and peptide hormone receptors [4]), converting this stress response from cytoprotective to cytotoxic. Experimental evidence supports direct interaction of ErSO-like compounds with ERα, although the binding is not competitive with estrogen [1]. Interaction of ErSO-like compounds with the cation selective channel TRPM4 (transient receptor potential cation channel subfamily M member 4) is proposed to induce osmotic stress that leads to sustained lethal a-UPR hyperactivation [3].
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 4
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 52.57
Molecular weight 434.31
XLogP 2.71
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 C1=CC(=C2C(=C1)[C@](C3=CC=C(C=C3)O)(C(=O)N2)N4CC(C(C4)(F)F)(F)F)C(F)(F)F
Isomeric SMILES OC1=CC=C(C=C1)[C@]2(N3CC(F)(F)C(F)(F)C3)C(=O)NC4=C2C=CC=C4C(F)(F)F
InChI InChI=1S/C19H13F7N2O2/c20-16(21)8-28(9-17(16,22)23)18(10-4-6-11(29)7-5-10)12-2-1-3-13(19(24,25)26)14(12)27-15(18)30/h1-7,29H,8-9H2,(H,27,30)/t18-/m1/s1
InChI Key PSTKCYQKNLKUBN-GOSISDBHSA-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
IC50 for ErSO-TFPy is 4-5 nM as determined in viability assays using ERα+ve MCF-7 cells [2]. In mice a single dose of ErSO-TFPy was able to completely eradicate sensitive tumours, with no regrowth detected after extended periods of observation, including in a fulvestrant-resistant, ERα-mutant, patient-derived xenograft model.