compound A [WO2022027058A1]   Click here for help

GtoPdb Ligand ID: 11904

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: This compound in an IRAK4 degrader (PROTAC) that is claimed in Kymera Therapeutics' patent WO2022027058A1 [1]. It is intended as a therapeutic for B-cell lymphomas that express oncogenic mutations in MYD88, e.g. the protein variant MYD88L265P. The cereblon binding portion of the molecule is based on the structure of the immunomodulatory imide drug (IMiD) lenalidomide. Compound A simultaneously promotes the degradation of IRAK4 and the zinc-finger transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), and this mechanism synergistically targets key pro-survival pathways in B-cell lymphomas (MYD88-NFκB and IRF4-Type 1 interferon) to enhance anti-tumour activity.
Kymera have an IRAK4/IMDi degrader (KT-413) in their clinical pipeline, but the name-to-structure has not been disclosed.
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 CDK toolkit. 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 13
Hydrogen bond donors 4
Rotatable bonds 13
Topological polar surface area 202.17
Molecular weight 871.33
XLogP 4.66
No. Lipinski's rules broken 2
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)cccc2NCCC1CC2(C1)CN(C2)C[C@@H]1CC[C@H](CC1)c1sc2c(n1)cc(c(c2)NC(=O)c1cccc(n1)C(F)(F)F)C(O)(C)C
Isomeric SMILES CC(C)(O)c1cc2c(sc(n2)[C@H]2CC[C@H](CN3CC4(CC(CCNc5c6C(=O)N(C7CCC(=O)NC7=O)C(=O)c6ccc5)C4)C3)CC2)cc1NC(=O)c1cccc(n1)C(F)(F)F
InChI InChI=1S/C45H48F3N7O6S/c1-43(2,61)28-17-32-34(18-31(28)51-38(57)30-7-4-8-35(50-30)45(46,47)48)62-40(52-32)26-11-9-24(10-12-26)21-54-22-44(23-54)19-25(20-44)15-16-49-29-6-3-5-27-37(29)42(60)55(41(27)59)33-13-14-36(56)53-39(33)58/h3-8,17-18,24-26,33,49,61H,9-16,19-23H2,1-2H3,(H,51,57)(H,53,56,58)/t24-,26-,33?
InChI Key WDRJGMSUTPVXDH-KBOGUJPVSA-N
Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
IUPAC Name Click here for help
N-[2-[4-[[6-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethyl]-2-azaspiro[3.3]heptan-2-yl]methyl]cyclohexyl]-5-(2-hydroxypropan-2-yl)-1,3-benzothiazol-6-yl]-6-(trifluoromethyl)pyridine-2-carboxamide
Database Links Click here for help
GtoPdb PubChem SID 461663459
PubChem CID 156506667
Search Google for chemical match using the InChIKey WDRJGMSUTPVXDH-KBOGUJPVSA-N
Search Google for chemicals with the same backbone WDRJGMSUTPVXDH
UniChem Compound Search for chemical match using the InChIKey WDRJGMSUTPVXDH-KBOGUJPVSA-N
UniChem Connectivity Search for chemical match using the InChIKey WDRJGMSUTPVXDH-KBOGUJPVSA-N