4QP2: Crystal Structure Of Erks In Complex With 5-chlorobenzo[d]oxazol-2- Amine

A fragment-based lead discovery approach was used to discover novel ERK2 inhibitors. The crystal structure of N-benzyl-9H-purin-6-amine 1 in complex with ERK2 elucidated its hinge-binding mode. In addition, the simultaneous binding of an imidazole molecule adjacent to 1 suggested a direction for fragment expansion. Structure-based core hopping applied to 1 led to 5H-pyrrolo[3,2-b]pyrazine (3) that afforded direct vectors to probe the pockets of interest while retaining the essential hinge binding elements. Utilizing the new vectors for SAR exploration, the new core 3 was quickly optimized to compound 39 resulting in a greater than 6600-fold improvement in potency.
PDB ID: 4QP2Download
MMDB ID: 132764
PDB Deposition Date: 2014/6/22
Updated in MMDB: 2015/12
Experimental Method:
x-ray diffraction
Resolution: 2.23  Å
Source Organism:
Similar Structures:
Biological Unit for 4QP2: monomeric; determined by author and by software (PISA)
Molecular Components in 4QP2
Label Count Molecule
Protein (1 molecule)
Mitogen-activated Protein Kinase 1(Gene symbol: MAPK1)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB