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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2D Structure
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Physico-chemical Properties
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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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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/)

Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
IUPAC Name Click here for help
3-[4-[1-[[(3S)-1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]pyrrolidin-3-yl]methyl]piperidin-4-yl]anilino]-5-piperidin-1-ylpyrazine-2-carboxamide
International Nonproprietary Names Click here for help
INN number INN
13078 zelebrudomide
Synonyms Click here for help
compound 28 [PMID: 38300987] | NX-2127 | NX2127
Database Links Click here for help
CAS Registry No. 2416131-46-7 (source: WHO INN record)
GtoPdb PubChem SID 500839900
PubChem CID 146559796
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