IRAK3 PROTAC 23   Click here for help

GtoPdb Ligand ID: 11785

Synonyms: compound 23 [PMID: 32803978]
Compound class: Synthetic organic
Comment: This molecule is aproteolysis-targeting chimera (PROTAC) degrader of interleukin 1 receptor associated kinase 3 (IRAK3) [1]. It promotes ternary complex formation between IRAK3 and the cereblon (CRBN) E3 ubiquitin ligase. IRAK3 is a regulatory protein that suppresses proinflammatory signalling in monocytes, macrophages, and neutrophils. Blocking IRAK3's immunosuppressive function is being investigated as an anti-tumour mechanism [2].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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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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 O=C1CCC(C(=O)N1)N1C(=O)c2c(C1=O)ccc(c2)N1CCN(CC1)CCC1CCN(CC1)C(=O)CCC(=O)N1CCN(CC1)[C@@H]1CC[C@@H](CC1)Nc1ncnn2c1c(cc2)C(C)C
Isomeric SMILES CC(c1c2n(ncnc2N[C@H]2CC[C@H](CC2)N2CCN(CC2)C(=O)CCC(=O)N2CCC(CC2)CCN2CCN(CC2)c2cc3c(cc2)C(=O)N(C3=O)C2C(=O)NC(=O)CC2)cc1)C
InChI InChI=1S/C47H63N11O6/c1-31(2)36-16-20-57-43(36)44(48-30-49-57)50-33-3-5-34(6-4-33)53-25-27-56(28-26-53)42(61)12-11-41(60)55-18-14-32(15-19-55)13-17-52-21-23-54(24-22-52)35-7-8-37-38(29-35)47(64)58(46(37)63)39-9-10-40(59)51-45(39)62/h7-8,16,20,29-34,39H,3-6,9-15,17-19,21-28H2,1-2H3,(H,48,49,50)(H,51,59,62)/t33-,34+,39?
InChI Key ZUODKONSNNHSAJ-AMLBMYBGSA-N
Bioactivity Comments
PROTAC 23 selectively degrades IRAK3 in THP1 cells (DC50 2 nM; maximum 98% degradation) [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
interleukin 1 receptor associated kinase 3 Hs Inhibitor Binding 8.3 pIC50 - 1
⤷ pIC50 8.3 (IC50 5x10-9 M) [1]
Description: LanthaScreen Eu IRAK3 binding displacement assay