| Structural highlights
Function
JAK1_HUMAN Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
Publication Abstract from PubMed
Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1: E966; JAK2: D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed.
Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2.,Labadie S, Dragovich PS, Barrett K, Blair WS, Bergeron P, Chang C, Deshmukh G, Eigenbrot C, Ghilardi N, Gibbons P, Hurley CA, Johnson A, Kenny JR, Kohli PB, Kulagowski JJ, Liimatta M, Lupardus PJ, Mendonca R, Murray JM, Pulk R, Shia S, Steffek M, Ubhayakar S, Ultsch M, van Abbema A, Ward S, Zak M Bioorg Med Chem Lett. 2012 Oct 11. pii: S0960-894X(12)01275-9. doi:, 10.1016/j.bmcl.2012.10.008. PMID:23107482[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Labadie S, Dragovich PS, Barrett K, Blair WS, Bergeron P, Chang C, Deshmukh G, Eigenbrot C, Ghilardi N, Gibbons P, Hurley CA, Johnson A, Kenny JR, Kohli PB, Kulagowski JJ, Liimatta M, Lupardus PJ, Mendonca R, Murray JM, Pulk R, Shia S, Steffek M, Ubhayakar S, Ultsch M, van Abbema A, Ward S, Zak M. Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2. Bioorg Med Chem Lett. 2012 Oct 11. pii: S0960-894X(12)01275-9. doi:, 10.1016/j.bmcl.2012.10.008. PMID:23107482 doi:http://dx.doi.org/10.1016/j.bmcl.2012.10.008
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