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ACKNOWLEDGMENTS
We thank B. Andresen, D. Hesk, T. Ho, D. Levorse, N. Rivera,
and X. Song for generation of custom reagents and molecular
characterization needed for these studies; H. Hatch and
E. DiNunzio for support in developing certain biochemical and
cell-based assays used in this work; C. Li for assistance with
coordinating in vivo studies; and A. Beard, H.-Y. Kim, L. Nogle,
C. Pickens, J. Sauri, D. Sloman, D. Smith, and WuXi AppTec
for contributions to synthesis, purification, and characterization
of the molecules described herein. This research used resources
at the Industrial Macromolecular Crystallography Association
Collaborative Access Team (IMCA-CAT) beamline 17-ID, supported
by the companies of the Industrial Macromolecular Crystallography
Association through a contract with Hauptman-Woodward Medical
Research Institute. This research used resources of the Advanced
Photon Source, a U.S. Department of Energy (DOE) Office of
Science User Facility operated for the DOE Office of Science by
Argonne National Laboratory under contract no. DE-AC02-
06CH11357. We acknowledge the Paul Scherrer Institut, Villigen,
Switzerland, for provision of synchrotron radiation beamtime at
beamline PXI_X06SA of the Swiss Light Source.Funding:This
work was supported by Merck Sharp & Dohme Corp., a subsidiary
of Merck & Co., Inc., Kenilworth, NJ, USA.Author contributions:
B.-S.P., S.A.P., J.A.P., J.P.P., G.K.S., B.W.T., B.M.L., M.D.A.,
A.V.B., J.N.C., P.J.D., A.H., I.Ka., I.Kn., B.J.L., D.J.B., L.R., S.C., S.S.,
C.A.L., L.P., D.F.W., and G.H.A. conceived, designed, or planned
the studies. B.-S.P., S.A.P., J.A.P., J.P.P., G.K.S., M.D.A., A.V.B.,
Y.C., J.J., J.K., J.L., C.A.L., A.H., L.R., S.S., E.C.M., B.S., Y.M.,
B.C., W.C., Y.C., G.F., T.H., R.L., M.L., G.O., R.O., L.P., S.T., H.W.,
D.F.W., and S.X. contributed to the design and synthesis of
molecules and/or acquisition, analysis, or interpretation of
the data. B.-S.P., S.A.P., J.A.P., J.P.P., G.K.S., B.W.T., J.N.C., M.D.A.,
C.A.L., and D.F.W. drafted the manuscript. All authors critically
reviewed or revised the manuscript for intellectual content
and approved the final version.Competing interests:Merck &
Co., Inc., has filed patent applications related to this manuscript,
including: PCT International Patent Application nos. PCT/US2016/
046444, PCT/US2017/054688, PCT/US2017/066557, PCT/
US2018/044275, PCT/US2018/044276, and PCT/US2019/025088.
All authors are employees or former employees of Merck Sharp &
Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ,
USA, and may hold stock or stock options in Merck & Co., Inc.,
Kenilworth, NJ, USA.Data and materials availability:All data are
available in the main text or the supplementary materials. The
structure factors and coordinates have been deposited with the
Protein Data Bank (IDs 6UKM, 6UKU, 6UKV, 6UKW, 6UKX, 6UKY,
6UKZ, and 6UL0).SUPPLEMENTARY MATERIALS
science.sciencemag.org/content/369/6506/eaba6098/suppl/DC1
Materials and Methods
Supplementary Text S1 and S2
Figs. S1 to S11
Tables S1 to S6
References ( 24 – 39 )
View/request a protocol for this paper fromBio-protocol.17 December 2019; accepted 13 July 2020
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