5VP0

Discovery of Clinical Candidate N-{(1S)-1-[3-Fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	SYNCHROTRON
Source details	ALS BEAMLINE 5.0.2
Synchrotron site	ALS
Beamline	5.0.2
Temperature [K]	100
Detector technology	PIXEL
Collection date	2016-03-03
Detector	DECTRIS PILATUS3 S 6M
Wavelength(s)	0.970
Spacegroup name	C 1 2 1
Unit cell lengths	166.704, 74.265, 91.171
Unit cell angles	90.00, 109.77, 90.00

Refinement procedure

Resolution	30.000 - 2.200
R-factor	0.2125
Rwork	0.211
R-free	0.23600
Structure solution method	MOLECULAR REPLACEMENT
RMSD bond length	0.009
RMSD bond angle	1.379
Data reduction software	HKL-2000
Data scaling software	SCALEPACK
Phasing software	PHASER
Refinement software	REFMAC

Data quality characteristics

	Overall	Inner shell	Outer shell
Low resolution limit [Å]	50.000	50.000	2.240
High resolution limit [Å]	2.200	5.970	2.200
Rmerge	0.094	0.052	0.406
Rmeas	0.108	0.060	0.495
Rpim	0.052	0.029	0.279
Total number of observations	188142
Number of reflections	47983
<I/σ(I)>	6.6
Completeness [%]	90.6	99.9	44.5
Redundancy	3.9	4.3	2.3
CC(1/2)		0.996	0.851

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, HANGING DROP	7.5	293	30% PEG3350, 0.2M MgCl2, 0.1M Tris pH 7.5