ERD-308   Click here for help

GtoPdb Ligand ID: 10565

Synonyms: compound 32 [PMID: 30990042] | ERD308
Compound class: Synthetic organic
Comment: ERD-308 is a small-molecule ERα degrader that was designed using the proteolysis targeting chimeras (PROTAC) model [1]. It is a hybrid molecule that links together an ERα antagonist (a derivative of raloxifene) and a VHL ligand that engages the VHL E3 ligase to direct ERα receptors for ubiquitination and proteasomal degradation.
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 CDK toolkit. 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 5
Rotatable bonds 26
Topological polar surface area 247.34
Molecular weight 1003.42
XLogP 7.84
No. Lipinski's rules broken 3
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.

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Canonical SMILES CCN(CCOc1ccc(cc1)C(=O)c1c(sc2c1ccc(c2)O)c1ccc(cc1)O)CCCCCOCC(=O)NC(C(C)(C)C)C(=O)N1CC(CC1C(=O)NC(c1ccc(cc1)c1scnc1C)C)O
Isomeric SMILES CCN(CCOc1ccc(cc1)C(=O)c1c(sc2c1ccc(c2)O)c1ccc(cc1)O)CCCCCOCC(=O)N[C@@H](C(C)(C)C)C(=O)N1C[C@@H](C[C@H]1C(=O)N[C@H](c1ccc(cc1)c1scnc1C)C)O
InChI InChI=1S/C55H65N5O9S2/c1-7-59(26-28-69-43-22-17-37(18-23-43)49(65)48-44-24-21-41(62)30-46(44)71-51(48)39-15-19-40(61)20-16-39)25-9-8-10-27-68-32-47(64)58-52(55(4,5)6)54(67)60-31-42(63)29-45(60)53(66)57-34(2)36-11-13-38(14-12-36)50-35(3)56-33-70-50/h11-24,30,33-34,42,45,52,61-63H,7-10,25-29,31-32H2,1-6H3,(H,57,66)(H,58,64)/t34-,42+,45-,52+/m0/s1
InChI Key BQXUPNKLZNSUMC-YUQWMIPFSA-N
Bioactivity Comments
ERD-308 induces more complete ER degradation than the approved ER degrader (SERD) fulvestrant [1] which targets ERα for proteasome-dependent degradation but via a different mechanism (protein mis-folding) to PROTACs. SERDs only achieve partial degradation of the ER protein, whereas ERD-308 can induce almost complete ER degradation at concentrations as low as 5 nM in cell lines. The DC50 of ERD-308 for ERα is 0.17 nM in MCF-7 cells, and 0.43 nM in T47D cells. It binds the VHL protein with an IC50 of 196 nM.
Selectivity at nuclear hormone receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Estrogen receptor-α Hs Antagonist Antagonist - - - 1
⤷ [1]