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

doi: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

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

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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 language	English (US)
Pages (from-to)	3756-3759
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2009.04.124
State	Published - Jul 15 2009

All Science Journal Classification (ASJC) codes

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

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10.1016/j.bmcl.2009.04.124

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Lawrence, H. R., Li, Z., Richard Yip, M. L., Sung, S. S., Lawrence, N. J., McLaughlin, M. L., McManus, G. J., Zaworotko, M. J., Sebti, S. M., Chen, J., & Guida, W. C. (2009). Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking. Bioorganic and Medicinal Chemistry Letters, 19(14), 3756-3759. https://doi.org/10.1016/j.bmcl.2009.04.124

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

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 Sung, {Shen Shu} 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.}",

note = "Funding Information: We are grateful to the National Institutes of Health for supporting this research through Grants P01CA118210 and P30 CA076292-10.",

year = "2009",

month = jul,

day = "15",

doi = "10.1016/j.bmcl.2009.04.124",

language = "English (US)",

volume = "19",

pages = "3756--3759",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Lawrence, HR, Li, Z, Richard Yip, ML, Sung, SS, 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

TY - JOUR

T1 - Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking

AU - Lawrence, Harshani R.

AU - Li, Zhenyu

AU - Richard Yip, M. L.

AU - Sung, Shen Shu

AU - Lawrence, Nicholas J.

AU - McLaughlin, Mark L.

AU - McManus, Gregory J.

AU - Zaworotko, Michael J.

AU - Sebti, Saïd M.

AU - Chen, Jiandong

AU - Guida, Wayne C.

N1 - Funding Information: We are grateful to the National Institutes of Health for supporting this research through Grants P01CA118210 and P30 CA076292-10.

PY - 2009/7/15

Y1 - 2009/7/15

N2 - 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.

AB - 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.

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JF - Bioorganic and Medicinal Chemistry Letters

IS - 14

ER -

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

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