zelebrudomide   Click here for help

GtoPdb Ligand ID: 13490

Synonyms: compound 28 [PMID: 38300987] | NX-2127 | NX2127
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Zelebrudomide (NX-2127) is an orally bioactive PROTAC degrader of Bruton's tyrosine kinase (BTK) [1]. It contains a BTK-binding moiety linked to a thalidomide-based cereblon (CRBN) engaging moiety. Zelebrudomide acts as a dual PROTAC (through recruitment of cereblon) and molecular glue (degradation of the neosubstrate transcription factors IKZF1/Ikaros and IKZF3/Aiolos). This combined action targets BTK on B cells, and boosts T cell activity, and is predicted to offer an improved mechanism to treat B cell malignancies, even in the presence of BTK mutations that confer resistance to clinically used kinase inhibitor drugs.

The INN record notes that one of the bonds can exist as R or S epimers, so we depict this bond without specified stereo to represent the racemate. The other rotational bond is S.
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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

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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 14
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 173.11
Molecular weight 719.83
XLogP 0.83
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 C1CCN(CC1)C2=NC(=C(C(=O)N)N=C2)NC3=CC=C(C=C3)C4CCN(CC4)C[C@@H]5CCN(C5)C6=CC=C7C(=C6)C(=O)N(C8CCC(=O)NC8=O)C7=O
Isomeric SMILES NC(=O)C1=NC=C(N=C1NC2=CC=C(C=C2)C3CCN(C[C@@H]4CCN(C4)C5=CC6=C(C=C5)C(=O)N(C7CCC(=O)NC7=O)C6=O)CC3)N8CCCCC8
InChI InChI=1S/C39H45N9O5/c40-35(50)34-36(43-32(21-41-34)46-15-2-1-3-16-46)42-27-6-4-25(5-7-27)26-13-17-45(18-14-26)22-24-12-19-47(23-24)28-8-9-29-30(20-28)39(53)48(38(29)52)31-10-11-33(49)44-37(31)51/h4-9,20-21,24,26,31H,1-3,10-19,22-23H2,(H2,40,50)(H,42,43)(H,44,49,51)/t24-,31?/m0/s1
InChI Key XLWJWCMQMBVNSG-ACXKHFGCSA-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/)
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Canonical SMILES Download
Isomeric SMILES Download
InChI standard identifier Download
InChI standard key Download

Molecular structure representations generated using Open Babel