Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications. ACS Chem Biol. 2019 Nov 15;14(11):2430-2440. PMID:31059647 DOI:10.1021/acschembio.8b01083
Target: BRD4 Bromodomain-containing protein 4 O60885 Homo sapiens
E3 ligase: RNF4
E3 binder: CCW 16
SMILES: show
ClCC(N(CC1=CC=CC=C1)C2=CC=C(OC3=CC=C(OC)C=C3)C=C2)=O

Ligand Name: JQ1
Ligand PDB Id: JQ1
PDB with Ligand: 3MXF
SMILES: show
Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)OC(C)(C)C)c1nnc(C)n1-2

Calculated Values
MW: 821.83
Hbond donors: 1
Hbond acceptors: 9
cLogP: 9.73
TPSA: 110.94

SMILES: show
ClCC(N(CC1=CC=CC=C1)C2=CC=C(OC3=CC=C(OCCCCNC(C[C@@H](C4=NN=C(N4C5=C6C(C)=C(S5)C)C)N=C6C(C=C7)=CC=C7Cl)=O)C=C3)C=C2)=O

Linker type: Alkane
Incubation time (hours): 3
Cells: 231MFP breast cancer cells, HeLa
IC50: = 0.54 μM
Dmax: > 50 %
Tested a non-binding E3 control?: No
Tested competition with ligand?: Yes
Tested proteaseome inhibitor?: Yes
Proteomics data available?: Yes
Tested engagement in cells?: No
Off-targets reported?: Yes, MT2A, ZC2HC1A, ZNF367, and ENSA were also down-regulated
Contributed by: Yangwode Jing