6H3K
Introduction of a methyl group curbs metabolism of pyrido[3,4-d]pyrimidine MPS1 inhibitors and enables the discovery of the Phase 1 clinical candidate BOS172722.
Experimental procedure
| Experimental method | SINGLE WAVELENGTH |
| Source type | SYNCHROTRON |
| Source details | DIAMOND BEAMLINE I04-1 |
| Synchrotron site | Diamond |
| Beamline | I04-1 |
| Temperature [K] | 100 |
| Detector technology | PIXEL |
| Collection date | 2015-08-07 |
| Detector | DECTRIS PILATUS 2M |
| Wavelength(s) | 0.9282 |
| Spacegroup name | I 2 2 2 |
| Unit cell lengths | 71.624, 107.644, 114.683 |
| Unit cell angles | 90.00, 90.00, 90.00 |
Refinement procedure
| Resolution | 41.330 - 2.480 |
| R-factor | 0.209 |
| Rwork | 0.208 |
| R-free | 0.23100 |
| Structure solution method | MOLECULAR REPLACEMENT |
| RMSD bond length | 0.009 |
| RMSD bond angle | 1.010 |
| Data reduction software | XDS |
| Data scaling software | Aimless |
| Phasing software | PHASER (2.5.7) |
| Refinement software | BUSTER |
Data quality characteristics
| Overall | Inner shell | Outer shell | |
| Low resolution limit [Å] | 60.520 | 60.520 | 2.740 |
| High resolution limit [Å] | 2.670 | 11.940 | 2.670 |
| Rmerge | 0.092 | 0.039 | 1.780 |
| Rmeas | 0.101 | 0.043 | 1.936 |
| Rpim | 0.039 | 0.017 | 0.755 |
| Total number of observations | 83046 | 927 | 6094 |
| Number of reflections | 12793 | 170 | 941 |
| <I/σ(I)> | 11.7 | 38.1 | 1 |
| Completeness [%] | 99.7 | 98.5 | 99.7 |
| Redundancy | 6.5 | 5.5 | 6.5 |
| CC(1/2) | 0.998 | 0.998 | 0.622 |
Crystallization Conditions
| crystal ID | method | pH | temperature | details |
| 1 | VAPOR DIFFUSION, SITTING DROP | 7.5 | 291.15 | 0.1 M Bis-Tris propane; 0.1 M MgCl2 0.1 M Sodium formate 18-26% PEG3350 |
