Synthesis and Target Identification of Hymenialdisine Analogs
Yongqin Wan
1
,
Wooyoung Hur
1
,
Charles H. Cho
2
,
Yi Liu
1
,
Francisco J. Adrian
1
,
Olivier Lozach
3
,
Stéphane Bach
3
,
Thomas E. Mayer
4
,
Doriano Fabbro
4
,
Laurent Meijer
3
,
N. Gray
1
1
Genomics Institute of the Novartis Research Foundation, Department of Chemistry, 10675 John Jay Hopkins Drive, San Diego, CA 92121 USA
|
3
CNRS, Cell Cycle Group, Station Biologique, B.P. 74, 29682 Roscoff cedex, Bretagne, France
|
4
Oncology Research, Novartis Pharma AG, CH-4002 Basel, Switzerland
|
Publication type: Journal Article
Publication date: 2004-02-01
PubMed ID:
15123286
Drug Discovery
Biochemistry
Molecular Biology
General Medicine
Pharmacology
Clinical Biochemistry
Molecular Medicine
Abstract
Hymenialdisine (HMD) is a sponge-derived natural product kinase inhibitor with nanomolar activity against CDKs, Mek1, GSK3beta, 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, PKCtheta, 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).
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121
Total citations:
121
Citations from 2024:
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(4%)
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GOST
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Wan Y. et al. Synthesis and Target Identification of Hymenialdisine Analogs // Chemistry & Biology. 2004. Vol. 11. No. 2. pp. 247-259.
GOST all authors (up to 50)
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Wan Y., Hur W., Cho C. H., Liu Y., Adrian F. J., Lozach O., Bach S., Mayer T. E., Fabbro D., Meijer L., Gray N. Synthesis and Target Identification of Hymenialdisine Analogs // Chemistry & Biology. 2004. Vol. 11. No. 2. pp. 247-259.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1016/j.chembiol.2004.01.015
UR - https://doi.org/10.1016/j.chembiol.2004.01.015
TI - Synthesis and Target Identification of Hymenialdisine Analogs
T2 - Chemistry & Biology
AU - Wan, Yongqin
AU - Hur, Wooyoung
AU - Cho, Charles H.
AU - Liu, Yi
AU - Adrian, Francisco J.
AU - Lozach, Olivier
AU - Bach, Stéphane
AU - Mayer, Thomas E.
AU - Fabbro, Doriano
AU - Meijer, Laurent
AU - Gray, N.
PY - 2004
DA - 2004/02/01
PB - Elsevier
SP - 247-259
IS - 2
VL - 11
PMID - 15123286
SN - 1074-5521
SN - 1879-1301
ER -
Cite this
BibTex (up to 50 authors)
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@article{2004_Wan,
author = {Yongqin Wan and Wooyoung Hur and Charles H. Cho and Yi Liu and Francisco J. Adrian and Olivier Lozach and Stéphane Bach and Thomas E. Mayer and Doriano Fabbro and Laurent Meijer and N. Gray},
title = {Synthesis and Target Identification of Hymenialdisine Analogs},
journal = {Chemistry & Biology},
year = {2004},
volume = {11},
publisher = {Elsevier},
month = {feb},
url = {https://doi.org/10.1016/j.chembiol.2004.01.015},
number = {2},
pages = {247--259},
doi = {10.1016/j.chembiol.2004.01.015}
}
Cite this
MLA
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Wan, Yongqin, et al. “Synthesis and Target Identification of Hymenialdisine Analogs.” Chemistry & Biology, vol. 11, no. 2, Feb. 2004, pp. 247-259. https://doi.org/10.1016/j.chembiol.2004.01.015.
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