6P5P

Discovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidinone-Based Cdc7 inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Anti-Tumor Agent

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	CCD
Collection date	2011-11-23
Detector	ADSC QUANTUM 315r
Wavelength(s)	0.97648
Spacegroup name	P 1 21 1
Unit cell lengths	89.171, 146.438, 111.300
Unit cell angles	90.00, 97.13, 90.00

Refinement procedure

Resolution	25.000 - 3.300
R-factor	0.2073
Rwork	0.206
R-free	0.23570
Structure solution method	MOLECULAR REPLACEMENT
Starting model (for MR)	2f2u
RMSD bond length	0.007
RMSD bond angle	1.327
Data reduction software	HKL-2000
Data scaling software	HKL-2000
Phasing software	PHASER
Refinement software	REFMAC (5.8.0238)

Data quality characteristics

	Overall	Inner shell	Outer shell
Low resolution limit [Å]	50.000	50.000	3.360
High resolution limit [Å]	3.300	8.940	3.300
Rmerge	0.147	0.033	0.890
Total number of observations	180093
Number of reflections	42899	2207	2082
<I/σ(I)>	5.9
Completeness [%]	99.9	100	99.6
Redundancy	4.2	4.2	4.1

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, SITTING DROP	5.2	293	0.8 M trisodium citrate, 0.1 M citrate, pH 5.2, Silver Bullets Bio B12 (0.025% thymidine-5'-triphosphate sodium salt, 0.025% alpha-ketoglutaric acid disodium salt, 0.025% 2-nitrophenyl beta-D-galactopyranoside, 0.025% cis-aconitic acid, 0.002 M HEPES sodium, pH 6.8)