Identification of novel SAR properties of the Jak2 small molecule inhibitor G6: significance of the para-hydroxyl orientation.
In this study, we analyzed the structure-activity relationship properties of the small molecule Jak2 inhibitor G6. We synthesized a set of derivatives containing the native para-hydroxyl structure or an alternative meta-hydroxyl structure and examined their Jak2 inhibitory properties. We found that the para-hydroxyl derivative known as NB15 had excellent Jak2 inhibitory properties in silico, in vitro, and ex vivo when compared with meta-hydroxyl derivatives. These results indicate that NB15 is a potent derivative of the Jak2 inhibitor G6, and that maintaining the para-hydroxyl orientation of G6 is critical for its Jak2 inhibitory potential.
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.
Rebekah
R
Baskin
Meghanath
M
Gali
Sung O
SO
Park
Zhizhuang Joe
ZJ
Zhao
György M
GM
Keseru
Kirpal S
KS
Bisht
Peter P
PP
Sayeski
D000818:Animals; D001596:Benzylamines / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006900:Hydroxylation; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001596:Benzylamines; D054852:Small Molecule Libraries; D013267:Stilbenes; D053614:Janus Kinase 2