6TPD

Fragment-based discovery of pyrazolopyridones as JAK1 inhibitors with excellent subtype selectivity

Experimental procedure

Experimental method	SINGLE WAVELENGTH
Source type	SYNCHROTRON
Source details	DIAMOND BEAMLINE I02
Synchrotron site	Diamond
Beamline	I02
Temperature [K]	100
Detector technology	PIXEL
Collection date	2015-01-23
Detector	DECTRIS PILATUS3 6M
Wavelength(s)	0.97949
Spacegroup name	C 1 2 1
Unit cell lengths	107.411, 69.669, 50.798
Unit cell angles	90.00, 98.45, 90.00

Refinement procedure

Resolution	53.180 - 1.990
R-factor	0.22599
Rwork	0.223
R-free	0.27759
Structure solution method	MOLECULAR REPLACEMENT
Starting model (for MR)	5l3a
RMSD bond length	0.009
RMSD bond angle	1.377
Data reduction software	xia2
Data scaling software	Aimless
Phasing software	PHASER (5.8.0253)
Refinement software	REFMAC (5.8.0258)

Data quality characteristics

	Overall	Outer shell
Low resolution limit [Å]	53.180	2.090
High resolution limit [Å]	1.990	1.990
Rmeas	0.181	0.887
Number of reflections	25481	3357
<I/σ(I)>	7.7	3.3
Completeness [%]	99.9
Redundancy	3.3

Crystallization Conditions

crystal ID	method	pH	temperature	details
1	VAPOR DIFFUSION, HANGING DROP		277	2.1M Na Malonate pH 6.0/6.5, 0.1M glycine pH 8.2