Identification and Characterization of a Blood–Brain Barrier Penetrant Inositol Hexakisphosphate Kinase (IP6K) Inhibitor
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https://figshare.com/articles/dataset/Identification_and_Characterization_of_a_Blood_Brain_Barrier_Penetrant_Inositol_Hexakisphosphate_Kinase_IP6K_Inhibitor/26489470
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资源简介：
Inositol hexakisphosphate kinases
(IP6Ks) have been studied
for
their role in glucose homeostasis, metabolic disease, fatty liver
disease, chronic kidney disease, neurological development, and psychiatric
disease. IP6Ks phosphorylate inositol hexakisphosphate (IP6) to the
pyrophosphate, 5-diphosphoinositol-1,2,3,4,6-pentakisphosphate (5-IP7).
Most of the currently known potent IP6K inhibitors contain a critical
carboxylic acid which limits blood–brain barrier (BBB) penetration.
In this work, the synthesis and testing of a variety of carboxylic
acid isosteres resulted in several new compounds with improved BBB
penetration. The most promising compound has an IP6K1 IC50 of 16 nM with an improved brain/plasma ratio and a favorable pharmacokinetic
profile. This series of brain penetrant compounds may be used to investigate
the role of IP6Ks in CNS disorders.
创建时间：
2024-08-03
