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Synthesis and in vivo activity of MK2 and MK2 substrate-selective p38alpha(MAPK) inhibitors in Werner syndrome cells.

Abstract：

:A benzopyranopyridine inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2) is prepared rapidly and efficiently in one step using microwave dielectric heating, whereas a substrate-selective p38 MAPK inhibitor was prepared using conventional heating techniques. The former had MK2 inhibitory activity above 2.5 microM concentration, whereas the latter showed no MK2 inhibition at 10 microM. However, rather than rescuing the reduced cellular growth rate and aged morphology of hTERT-immortalised WS dermal fibroblasts, both induce a state resembling stress-induced cellular senescence, suggesting that these inhibitors may have limited therapeutic use.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Davis T,Bagley MC,Dix MC,Murziani PG,Rokicki MJ,Widdowson CS,Zayed JM,Bachler MA,Kipling D

doi

10.1016/j.bmcl.2007.10.036

subject

Has Abstract

pub_date

2007-12-15 00:00:00

pages

6832-5

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)01205-X

journal_volume

17

pub_type

杂志文章

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