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Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking

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Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking. / Smith, Sarah A.; Sessions, Richard B.; Shoemark, Deborah K.; Williams, Christopher; Ebrahimighaei, Reza; McNeill, Madeleine C.; Crump, Matthew P.; McKay, Tristan R.; Harris, Gemma; Newby, Andrew C.; Bond, Mark.

In: Journal of Medicinal Chemistry, Vol. 62, No. 3, 14.02.2019, p. 1291-1305.

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@article{b80270f738384386b3d2304bfaa18deb,
title = "Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking",
abstract = "The Hippo pathway is an important regulator of cell growth, proliferation, and migration. TEAD transcription factors, which lie at the core of the Hippo pathway, are essential for regulation of organ growth and wound repair. Dysregulation of TEAD and its regulatory cofactor Yes-associated protein (YAP) have been implicated in numerous human cancers and hyperproliferative pathological processes. Hence, the YAP-TEAD complex is a promising therapeutic target. Here, we use in silico molecular docking using Bristol University Docking Engine to screen a library of more than 8 million druglike molecules for novel disrupters of the YAP-TEAD interaction. We report the identification of a novel compound (CPD3.1) with the ability to disrupt YAP-TEAD protein-protein interaction and inhibit TEAD activity, cell proliferation, and cell migration. The YAP-TEAD complex is a viable drug target, and CPD3.1 is a lead compound for the development of more potent TEAD inhibitors for treating cancer and other hyperproliferative pathologies.",
keywords = "Synthetic biology",
author = "Smith, {Sarah A.} and Sessions, {Richard B.} and Shoemark, {Deborah K.} and Christopher Williams and Reza Ebrahimighaei and McNeill, {Madeleine C.} and Crump, {Matthew P.} and McKay, {Tristan R.} and Gemma Harris and Newby, {Andrew C.} and Mark Bond",
year = "2019",
month = "2",
day = "14",
doi = "10.1021/acs.jmedchem.8b01402",
language = "English",
volume = "62",
pages = "1291--1305",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

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TY - JOUR

T1 - Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking

AU - Smith, Sarah A.

AU - Sessions, Richard B.

AU - Shoemark, Deborah K.

AU - Williams, Christopher

AU - Ebrahimighaei, Reza

AU - McNeill, Madeleine C.

AU - Crump, Matthew P.

AU - McKay, Tristan R.

AU - Harris, Gemma

AU - Newby, Andrew C.

AU - Bond, Mark

PY - 2019/2/14

Y1 - 2019/2/14

N2 - The Hippo pathway is an important regulator of cell growth, proliferation, and migration. TEAD transcription factors, which lie at the core of the Hippo pathway, are essential for regulation of organ growth and wound repair. Dysregulation of TEAD and its regulatory cofactor Yes-associated protein (YAP) have been implicated in numerous human cancers and hyperproliferative pathological processes. Hence, the YAP-TEAD complex is a promising therapeutic target. Here, we use in silico molecular docking using Bristol University Docking Engine to screen a library of more than 8 million druglike molecules for novel disrupters of the YAP-TEAD interaction. We report the identification of a novel compound (CPD3.1) with the ability to disrupt YAP-TEAD protein-protein interaction and inhibit TEAD activity, cell proliferation, and cell migration. The YAP-TEAD complex is a viable drug target, and CPD3.1 is a lead compound for the development of more potent TEAD inhibitors for treating cancer and other hyperproliferative pathologies.

AB - The Hippo pathway is an important regulator of cell growth, proliferation, and migration. TEAD transcription factors, which lie at the core of the Hippo pathway, are essential for regulation of organ growth and wound repair. Dysregulation of TEAD and its regulatory cofactor Yes-associated protein (YAP) have been implicated in numerous human cancers and hyperproliferative pathological processes. Hence, the YAP-TEAD complex is a promising therapeutic target. Here, we use in silico molecular docking using Bristol University Docking Engine to screen a library of more than 8 million druglike molecules for novel disrupters of the YAP-TEAD interaction. We report the identification of a novel compound (CPD3.1) with the ability to disrupt YAP-TEAD protein-protein interaction and inhibit TEAD activity, cell proliferation, and cell migration. The YAP-TEAD complex is a viable drug target, and CPD3.1 is a lead compound for the development of more potent TEAD inhibitors for treating cancer and other hyperproliferative pathologies.

KW - Synthetic biology

UR - http://www.scopus.com/inward/record.url?scp=85061630395&partnerID=8YFLogxK

U2 - 10.1021/acs.jmedchem.8b01402

DO - 10.1021/acs.jmedchem.8b01402

M3 - Article

C2 - 30640473

AN - SCOPUS:85061630395

VL - 62

SP - 1291

EP - 1305

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -