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- W2048652222 abstract "Hymenialdisine (HMD) is a sponge-derived natural product kinase inhibitor with nanomolar activity against CDKs, Mek1, GSK3β, and CK1 and micromolar activity against Chk1. In order to explore the broader application of the pyrrolo[2,3-c]azepine skeleton of HMD as a general kinase inhibitory scaffold, we searched for additional protein targets using affinity chromatography in conjunction with the synthesis of diverse HMD analogs and profiled HMD against a panel of 60 recombinant enzymes. This effort has led to nanomolar to micromolar inhibitors of 11 new targets including p90RSK, KDR, c-Kit, Fes, MAPK1, PAK2, PDK1, PKCθ, PKD2, Rsk1, and SGK. The synthesis of HMD analogs has resulted in the identification of compounds with enhanced and/or dramatically altered selectivities relative to HMD (28n) and in molecules with antiproliferative activities 30-fold higher than HMD (28p)." @default.
- W2048652222 created "2016-06-24" @default.
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- W2048652222 date "2004-02-01" @default.
- W2048652222 modified "2023-10-18" @default.
- W2048652222 title "Synthesis and Target Identification of Hymenialdisine Analogs" @default.
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- W2048652222 doi "https://doi.org/10.1016/j.chembiol.2004.01.015" @default.
- W2048652222 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15123286" @default.
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