4C62: Inhibitors Of Jak2 Kinase Domain

Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.
PDB ID: 4C62Download
MMDB ID: 116463
PDB Deposition Date: 2013/9/17
Updated in MMDB: 2017/06
Experimental Method:
x-ray diffraction
Resolution: 2.75  Å
Source Organism:
Similar Structures:
Biological Unit for 4C62: monomeric; determined by author and by software (PISA)
Molecular Components in 4C62
Label Count Molecule
Protein (1 molecule)
Tyrosine-protein Kinase Jak2(Gene symbol: JAK2)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

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