5O83

Discovery of CDZ173 (leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	6.8	290	Equal volumes of reservoir solution (43.3 mM NaNO4, 43.3 mM AS, 43.3 mM Na2HPO4, 20%glycerol, 12% PEG4000, 0.1M imidazole pH6.8) were mixed with protein

Crystal Properties
Matthews coefficient	Solvent content
2.39	48.59

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 142.12	α = 90
b = 63.99	β = 102.89
c = 116.54	γ = 90

Symmetry
Space Group	C 1 2 1

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	PIXEL	DECTRIS PILATUS3 S 6M		2010-08-07	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SLS BEAMLINE X10SA	1.00000	SLS	X10SA

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	Net I Over Average Sigma (I)	Redundancy	Number Reflections (All)	Number Reflections (Observed)	Observed Criterion Sigma (F)	Observed Criterion Sigma (I)	B (Isotropic) From Wilson Plot
1	2.9	58.1	99	9.7	3.4		22803			84.96

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Resolution (High)	Resolution (Low)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION		THROUGHOUT	2.9	58.1	22803	1141	99.5	0.233	0.23	0.274	RANDOM	55.17

Temperature Factor Modeling
Anisotropic B[1][1]	Anisotropic B[1][2]	Anisotropic B[1][3]	Anisotropic B[2][2]	Anisotropic B[2][3]	Anisotropic B[3][3]
0.4383		4.1013	-15.0837		14.6454

RMS Deviations
Key	Refinement Restraint Deviation
t_other_torsion	18.09
t_omega_torsion	2.21
t_angle_deg	1
t_bond_d	0.009
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it

RMS Deviations
Key	Refinement Restraint Deviation
t_other_torsion	18.09
t_omega_torsion	2.21
t_angle_deg	1
t_bond_d	0.009
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it
t_nbd
t_improper_torsion
t_chiral_improper_torsion
t_sum_occupancies
t_utility_distance
t_utility_angle
t_utility_torsion
t_ideal_dist_contact

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	5672
Nucleic Acid Atoms
Solvent Atoms	55
Heterogen Atoms	32

Software

Software
Software Name	Purpose
BUSTER	refinement
XDS	data reduction
XSCALE	data scaling
PHASER	phasing

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.