3E63

Fragment based discovery of JAK-2 inhibitors

Summary for 3E63

• Entry DOI: 10.2210/pdb3e63/pdb
• Related: 3E62 3E64
• Descriptor: Tyrosine-protein kinase JAK2, 5-phenyl-1H-indazol-3-amine (3 entities in total)
• Functional Keywords: drug discovery, jak2, fragment based, atp-binding, disease mutation, kinase, membrane, nucleotide-binding, phosphoprotein, proto-oncogene, sh2 domain, transferase, tyrosine-protein kinase
• Biological source: Homo sapiens (human)
• Cellular location: Endomembrane system; Peripheral membrane protein (By similarity): O60674
• Total number of polymer chains: 1
• Total formula weight: 34887.74

Authors

Antonysamy, S.,Fang, W.,Hirst, G.,Park, F.,Russell, M.,Smyth, L.,Sprengeler, P.,Stappenbeck, F.,Steensma, R.,Thompson, D.A.,Wilson, M.,Wong, M.,Zhang, A.,Zhang, F. (deposition date: 2008-08-14, release date: 2008-10-14, Last modification date: 2012-02-08)

Primary citation

Antonysamy, S.,Hirst, G.,Park, F.,Sprengeler, P.,Stappenbeck, F.,Steensma, R.,Wilson, M.,Wong, M.
Fragment-based discovery of JAK-2 inhibitors.
Bioorg.Med.Chem.Lett., 19:279-282, 2009

PubMed Abstract: Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.

PubMed: 19019674
DOI: 10.1016/j.bmcl.2008.08.064

Experimental method

X-RAY DIFFRACTION (1.9 Å)