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PHTPP-1304   Click here for help

GtoPdb Ligand ID: 12144

Compound class: Synthetic organic
Comment: PHTPP-1304 is a novel protein degrader [1-2]. It binds to the estrogen receptor β via the ERβ antagonist PHTPP domain, and simultaneously to the autophagy receptor p62, to target the ERβ . This class of degrader is called an AUTOphagy-TArgeting Chimera, or AUTOTAC. AUTOTACs can be designed to target proteins of interest to autophagic membranes where they undergo lysosomal degradation, in a proteasome-independent manner.

PHTPP-1304 is commercially available from our sponsors

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 6
Hydrogen bond donors 2
Rotatable bonds 27
Topological polar surface area 117.83
Molecular weight 944.36
XLogP 9.98
No. Lipinski's rules broken 2

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 O[C@@H](COc1ccc(c(c1)OCCCc1ccccc1)OCc1ccccc1)CNCCOCCOCCOc1ccc(cc1)c1c(nn2c1nc(cc2C(F)(F)F)C(F)(F)F)c1ccccc1
Isomeric SMILES O[C@H](CNCCOCCOCCOc1ccc(cc1)c1c2nc(cc(n2nc1c1ccccc1)C(F)(F)F)C(F)(F)F)COc1cc(OCCCc2ccccc2)c(OCc2ccccc2)cc1
InChI InChI=1S/C51H50F6N4O7/c52-50(53,54)45-32-46(51(55,56)57)61-49(59-45)47(48(60-61)39-16-8-3-9-17-39)38-18-20-41(21-19-38)65-30-29-64-28-27-63-26-24-58-33-40(62)35-67-42-22-23-43(68-34-37-13-6-2-7-14-37)44(31-42)66-25-10-15-36-11-4-1-5-12-36/h1-9,11-14,16-23,31-32,40,58,62H,10,15,24-30,33-35H2/t40-/m1/s1
InChI Key RFLBGKJLIDOOAA-RRHRGVEJSA-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
PHTPP-1304 has a half-degrading concentration (DC50) for ERβ of ~2 nM in HEK293T cells. Binding affinity for ERβ is expected to be similar to that for the parent antagonist PHTPP.