Reporting summary
Further information on research design is available in the Nature
Research Reporting Summary linked to this paper.
Data availability
The RNA-seq and ChIP–seq dataset can be accessed from GEO
(accession numbers GSE118152, GSE118247 and GSE130269). Crystal
coordinates and X-ray diffraction data were deposited in the Protein
Data Bank with the accession numbers 6E6J and 6ONY.
Acknowledgements We thank Z. Zha for technical assistance with ChIP–seq data analysis. For
X-ray crystallography, use of the IMCA-CAT beamline 17-ID at the Advanced Photon Source was
supported by the companies of the Industrial Macromolecular Crystallography Association
through a contract with Hauptman-Woodward Medical Research Institute. Use of the
Advanced Photon Source was supported by the US Department of Energy, Office of Science,
Office of Basic Energy Sciences, under contract no. DE-AC02-06CH11357.
Author contributions K.F.M., G.S.S., L.W., S.F., J.K.P., D.L. and L.A.H. designed and synthesized the
compounds. E.J.F., D.W., M.H.B., X. Lin, X.H., P.H., L.Z. and R.J.B. performed in vitro studies
including cell proliferation, gene expression and ChIP studies. J.P.P., V.S., T.U., P.H., L.T.L., X. Lu and
E.J.F. analysed RNA-seq and ChIP–seq data. D.H.A. and G.M. performed in vivo efficacy studies.
C.H.P., K.L., L.B. and M.T. contributed to three-dimensional structure data generation and analysis.
S.C.P. and C.S. generated surface plasmon resonance-binding data. S.R.M., J.J.N. and S.L.F. carried
out rat toxicology studies. E.J.F., D.H.A., S.R.M., J.J.N., S.L.F., W.M.K., K.F.M., S.H.R., L.Z., W.M.K. and
Y.S. designed studies and interpreted results. E.J.F., K.F.M. and Y.S. wrote the paper.
Competing interests E.J.F., K.F.M., D.H.A., S.R.M., L.Z., M.H.B., G.S.S., L.W., J.P.P., V.S., X. Lin,
X.H., X. Lu, T.U., L.T.L., R.J.B., G.M., S.F., J.K.P., D.L., L.A.H., C.S., S.C.P., J.J.N., S.L.F., K.L., L.B., M.T.,
S.H.R., W.M.K. and Y.S. are employees of AbbVie. C.H.P., D.W. and P.H. were employees of
AbbVie at the time of the study. The design, study conduct and financial support for this
research were provided by AbbVie. AbbVie participated in the interpretation of data, review
and approval of the publication.
Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41586-020-
1930-8.
Correspondence and requests for materials should be addressed to Y.S.
Peer review information Nature thanks Arul Chinnaiyan, Stefan Knapp, William Pomerantz and
the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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