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

University of South Florida

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

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
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
Publication status	Published - 15 Jul 2009
Externally published	Yes

Keywords

Alphascreen™
Anticancer
Mdm2-p53
Protein-protein interaction
Virtual screening

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

@article{a432c0c12dff49979e526ad53f6465aa,

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.",

keywords = "Alphascreen{\texttrademark}, Anticancer, Mdm2-p53, Protein-protein interaction, Virtual screening",

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.}",

year = "2009",

month = jul,

day = "15",

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

language = "English",

volume = "19",

pages = "3756--3759",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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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.

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.

KW - Alphascreen™

KW - Anticancer

KW - Mdm2-p53

KW - Protein-protein interaction

KW - Virtual screening

UR - http://www.scopus.com/inward/record.url?scp=67649646649&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.04.124

DO - 10.1016/j.bmcl.2009.04.124

M3 - Article

C2 - 19457663

AN - SCOPUS:67649646649

SN - 0960-894X

VL - 19

SP - 3756

EP - 3759

JO - Bioorganic and Medicinal Chemistry Letters

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

Abstract

Keywords

UN SDGs

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