6UCS

Discovery and Structure-Based optimization of potent and selective WDR5 inhibitors containing a dihydroisoquinolinone bicyclic core

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	SYNCHROTRON
Source details	APS BEAMLINE 21-ID-G
Synchrotron site	APS
Beamline	21-ID-G
Temperature [K]	100
Detector technology	CCD
Collection date	2018-01-30
Detector	MARMOSAIC 300 mm CCD
Wavelength(s)	0.987
Spacegroup name	P 1
Unit cell lengths	46.566, 47.099, 68.984
Unit cell angles	89.06, 89.82, 74.18

Refinement procedure

Resolution	28.240 - 1.850
R-factor	0.1678
Rwork	0.167
R-free	0.19420
Structure solution method	MOLECULAR REPLACEMENT
Starting model (for MR)	6dy7
RMSD bond length	0.005
RMSD bond angle	1.001
Data reduction software	HKL-2000
Data scaling software	HKL-2000
Phasing software	PHASER
Refinement software	PHENIX (1.12_2829)

Data quality characteristics

	Overall	Outer shell
Low resolution limit [Å]	40.000	1.880
High resolution limit [Å]	1.850	1.850
Rmerge	0.057	0.352
Rmeas	0.082	0.329
Rpim	0.049	0.207
Number of reflections	44095	2031
<I/σ(I)>	15.6	2.4
Completeness [%]	91.8	83
Redundancy	2.3	1.9
CC(1/2)	0.999	0.753

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, SITTING DROP		291	Bis-Tris, Ammonium Acetate, PEG 3350