BCL6 PROTAC 15   Click here for help

GtoPdb Ligand ID: 11778

Synonyms: compound 15 [PMID: 30335946]
Compound class: Synthetic organic
Comment: This is a bivalent proteolysis-targeting chimera (PROTAC) molecule that promotes the degradation of the BCL6 transcription repressor protein [1]. It comprises a BCL6 binding domain linked to a thalidomide warhead that targets the bound BCL6 to the E3 ubiquitin ligase cereblon (CRBN), and on to ubiquitin-mediated proteosomal degradation. PROTAC 15 was developed by AstraZeneca for potential to treat lymphomas that are derived from germinal center B cells. Although PROTAC 15 leads to BCL6 degradation in vitro, the degradation is incomplete, and this produces only a weak antiproliferative effect on target diffuse large B-cell lymphoma (DLBCL) cells.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 19
Hydrogen bond donors 3
Rotatable bonds 17
Topological polar surface area 240.47
Molecular weight 945.34
XLogP 0.88
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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Canonical SMILES O=C(CCC(=O)N1CCN2[C@H](C1)COCCOc1cc(Nc3nc2ncc3Cl)cc2c1N(C)C(=O)CC2)NCCCOCCOCCOc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O
Isomeric SMILES CN1C(=O)CCc2c1c1cc(Nc3nc(ncc3Cl)N3CCN(C[C@@H]3COCCO1)C(=O)CCC(=O)NCCCOCCOCCOc1cccc3c1C(=O)N(C1CCC(=O)NC1=O)C3=O)c2
InChI InChI=1S/C45H52ClN9O12/c1-52-37(58)10-6-27-22-28-23-34(40(27)52)67-21-19-65-26-29-25-53(13-14-54(29)45-48-24-31(46)41(49-28)51-45)38(59)11-9-35(56)47-12-3-15-63-16-17-64-18-20-66-33-5-2-4-30-39(33)44(62)55(43(30)61)32-7-8-36(57)50-42(32)60/h2,4-5,22-24,29,32H,3,6-21,25-26H2,1H3,(H,47,56)(H,48,49,51)(H,50,57,60)/t29-,32?/m1/s1
InChI Key YQWUMLVLLIWGQJ-UYEDPJPISA-N
Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
Synonyms Click here for help
compound 15 [PMID: 30335946]
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GtoPdb PubChem SID 458923813
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