dBRD9-A   Click here for help

GtoPdb Ligand ID: 10546

Compound class: Synthetic organic
Comment: This is an analogue of dBRD9, that was designed to achieve enhanced BRD9 degradation properties [1]. Like dBRD9 it is a PROTAC (proteolysis targeting chimera). dBRD9-A is a hybrid molecule that simultaneously engages the BRD9 bromodomain and recruits E3 ligase CRL4CRBN (using a pomalidomide-based module) to target BRD9 for destruction via E3 ligase-mediated ubiquitination and proteasomal degradation.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 11
Hydrogen bond donors 3
Rotatable bonds 19
Topological polar surface area 181.27
Molecular weight 779.36
XLogP 4.49
No. Lipinski's rules broken 2
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Canonical SMILES COc1cc(cc(c1CN(CC(=O)NCCCCCCCCNc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O)C)OC)c1cn(C)c(=O)c2c1ccnc2
Isomeric SMILES COc1cc(cc(c1CN(CC(=O)NCCCCCCCCNc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O)C)OC)c1cn(C)c(=O)c2c1ccnc2
InChI InChI=1S/C42H49N7O8/c1-47(23-31-34(56-3)20-26(21-35(31)57-4)30-24-48(2)40(53)29-22-43-19-16-27(29)30)25-37(51)45-18-10-8-6-5-7-9-17-44-32-13-11-12-28-38(32)42(55)49(41(28)54)33-14-15-36(50)46-39(33)52/h11-13,16,19-22,24,33,44H,5-10,14-15,17-18,23,25H2,1-4H3,(H,45,51)(H,46,50,52)
1. Brien GL, Remillard D, Shi J, Hemming ML, Chabon J, Wynne K, Dillon ET, Cagney G, Van Mierlo G, Baltissen MP et al.. (2018)
Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma.
Elife, 7: e41305. DOI: 10.7554/eLife.41305 [PMID:30431433]