1449276-76-9Relevant academic research and scientific papers
Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis
Ndubaku, Chudi O.,Crawford, Terry D.,Chen, Huifen,Boggs, Jason W.,Drobnick, Joy,Harris, Seth F.,Jesudason, Rajiv,McNamara, Erin,Nonomiya, Jim,Sambrone, Amy,Schmidt, Stephen,Smyczek, Tanya,Vitorino, Philip,Wang, Lan,Wu, Ping,Yeung, Stacey,Chen, Jinhua,Chen, Kevin,Ding, Charles Z.,Wang, Tao,Xu, Zijin,Gould, Stephen E.,Murray, Lesley J.,Ye, Weilan
, p. 913 - 918 (2015/08/24)
Diverse biological roles for mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) have necessitated the identification of potent inhibitors in order to study its function in various disease contexts. In particular, compounds that can be used to carry out such studies in vivo would be critical for elucidating the potential for therapeutic intervention. A structure-based design effort coupled with property-guided optimization directed at minimizing the ability of the inhibitors to cross into the CNS led to an advanced compound 13 (GNE-495) that showed excellent potency and good PK and was used to demonstrate in vivo efficacy in a retinal angiogenesis model recapitulating effects that were observed in the inducible Map4k4 knockout mice.
ISOQUINOLINE AND NAPHTHYRIDINE DERIVATIVES
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Page/Page column 79, (2013/08/15)
The invention provides novel compounds having the general formula(I) wherein A, R1 and R2 are as described herein, compositions including the compounds and use of the compounds for inhibiting angiogenesis by inhibition of MAP4K4.
