Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking

Harshani R. Lawrence, Zhenyu Li, M. L. Richard Yip, Shen-shu Sung, Nicholas J. Lawrence, Mark L. McLaughlin, Gregory J. McManus, Michael J. Zaworotko, Saïd M. Sebti, Jiandong Chen, Wayne C. Guida

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

NSC 333003 has been identified from the NCI Diversity Set as an inhibitor of the MDM2-p53 protein-protein interaction by in silico docking (virtual screening). Its potency and chemical characteristics render it well suited for lead optimization studies that can result in more potent analogs with improved drug-like properties. Its synthesis was achieved using an acid catalyzed condensation reaction from commercially available benzothiazole hydrazine and pyridyl phenyl ketone in refluxing methanol. Stereochemical implications for this compound are described.

Original languageEnglish (US)
Pages (from-to)3756-3759
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number14
DOIs
StatePublished - Jul 15 2009

Fingerprint

hydrazine
Computer Simulation
Throughput
Condensation reactions
Ketones
Methanol
Screening
Proteins
Acids
Pharmaceutical Preparations
benzothiazole
Lead

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Lawrence, Harshani R. ; Li, Zhenyu ; Richard Yip, M. L. ; Sung, Shen-shu ; Lawrence, Nicholas J. ; McLaughlin, Mark L. ; McManus, Gregory J. ; Zaworotko, Michael J. ; Sebti, Saïd M. ; Chen, Jiandong ; Guida, Wayne C. / Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking. In: Bioorganic and Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 14. pp. 3756-3759.
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abstract = "NSC 333003 has been identified from the NCI Diversity Set as an inhibitor of the MDM2-p53 protein-protein interaction by in silico docking (virtual screening). Its potency and chemical characteristics render it well suited for lead optimization studies that can result in more potent analogs with improved drug-like properties. Its synthesis was achieved using an acid catalyzed condensation reaction from commercially available benzothiazole hydrazine and pyridyl phenyl ketone in refluxing methanol. Stereochemical implications for this compound are described.",
author = "Lawrence, {Harshani R.} and Zhenyu Li and {Richard Yip}, {M. L.} and Shen-shu Sung and Lawrence, {Nicholas J.} and McLaughlin, {Mark L.} and McManus, {Gregory J.} and Zaworotko, {Michael J.} and Sebti, {Sa{\"i}d M.} and Jiandong Chen and Guida, {Wayne C.}",
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Lawrence, HR, Li, Z, Richard Yip, ML, Sung, S, Lawrence, NJ, McLaughlin, ML, McManus, GJ, Zaworotko, MJ, Sebti, SM, Chen, J & Guida, WC 2009, 'Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 14, pp. 3756-3759. https://doi.org/10.1016/j.bmcl.2009.04.124

Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking. / Lawrence, Harshani R.; Li, Zhenyu; Richard Yip, M. L.; Sung, Shen-shu; Lawrence, Nicholas J.; McLaughlin, Mark L.; McManus, Gregory J.; Zaworotko, Michael J.; Sebti, Saïd M.; Chen, Jiandong; Guida, Wayne C.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 14, 15.07.2009, p. 3756-3759.

Research output: Contribution to journalArticle

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AU - Lawrence, Harshani R.

AU - Li, Zhenyu

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AU - Sung, Shen-shu

AU - Lawrence, Nicholas J.

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AU - McManus, Gregory J.

AU - Zaworotko, Michael J.

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AU - Chen, Jiandong

AU - Guida, Wayne C.

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