Multi-parameter lead optimization to give an oral CHK1 inhibitor clinical candidate: (R)-5-((4-((morpholin-2-YLMETHYL)AMINO)-5- (TRIFLUOROMETHYL)PYRIDIN-2-YL)AMINO)PYRAZINE-2-carbonitrile (CCT245737)

Structure

x-ray diffraction · 1 distinct chain · 34% helix, 22% strand (DSSP).

Ligands and binding sites

• 5UY · methyl 6-[(5-cyanopyrazin-2-yl)amino]-4-[[(2~{R})-morpholin-2-yl]methylamino]pyridine-3-carboxylate · ligand · 2 copies · chains A
• EDO · 1,2-ethanediol · additive · 4 copies · chains A
• GOL · Glycerol · additive · 2 copies · chains A

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

1 pocket found on a 1 Å grid, 1 with a druggability of 0.5 or more.

Compared structures

• 5F4N · Multi-parameter lead optimization to give an oral CHK1 inhibitor clinical candidate… · the same entry in another collection · chain A against A, TM-score 1.00
• 2C3L · Identification of a buried pocket for potent and selective inhibition of CHK1: prediction… · a predicted model of the same protein · chain A against A, TM-score 0.99
• 2C3K · Identification of a buried pocket for potent and selective inhibition of CHK1: prediction… · a predicted model of the same protein · chain A against A, TM-score 0.99
• O14757 · AlphaFold monomer V2.0 prediction for SERINE/THREONINE-protein kinase CHK1 (O14757) · a predicted model of the same protein · chain A against A, TM-score 0.99
• 2C3J · Identification of a buried pocket for potent and selective inhibition of CHK1: prediction… · a predicted model of the same protein · chain A against A, TM-score 0.97

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt O14757
• Elsewhere: RCSB PDB 5F4N · PDBe 5F4N · UniProt O14757