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SH-26   Click here for help

GtoPdb Ligand ID: 14527

Synonyms: compound 26 [PMID: 42126822]
Compound class: Synthetic organic
Comment: SH-26 is a a first-in-class cereblon (CRBN)-recruiting PROTAC that is designed to induce degradation of prolyl hydroxylase domain enzyme 1 (PHD1; EGLN2) [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 17
Hydrogen bond donors 4
Rotatable bonds 20
Topological polar surface area 216.15
Molecular weight 751.79
XLogP -1.34
No. Lipinski's rules broken 3

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 CC1=C(C=CC(=C1)C#N)C2=CC(=CC3=NC=NN23)NCCC(=O)NCCOCCOCCOCCNC4=C5C(=CC=C4)C(=O)N(C6CCC(=O)NC6=O)C5=O
Isomeric SMILES O=C1N(C2CCC(NC2=O)=O)C(C3=CC=CC(NCCOCCOCCOCCNC(CCNC4=CC5=NC=NN5C(C6=C(C)C=C(C#N)C=C6)=C4)=O)=C31)=O
InChI InChI=1S/C38H41N9O8/c1-24-19-25(22-39)5-6-27(24)31-20-26(21-32-43-23-44-47(31)32)40-10-9-33(48)42-12-14-54-16-18-55-17-15-53-13-11-41-29-4-2-3-28-35(29)38(52)46(37(28)51)30-7-8-34(49)45-36(30)50/h2-6,19-21,23,30,40-41H,7-18H2,1H3,(H,42,48)(H,45,49,50)
InChI Key PHILWRQDFMAKGA-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
DC50 for SH-26-induced degradation of PHD1 is ~1 μM, with a Dmax of >75% [1]. In vivo, SH-26 down-regulates the immune response, providing protection against inflammation and tissue damage in a mouse model of acetaminophen (paracetamol)-induced acute liver injury [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
egl-9 family hypoxia inducible factor 2 Hs None Binding - - - 1
⤷ PROTAC degrader [1]