Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors

Meilan Huang; Zhuo Li; Dawei Li; Steven Walker; Caroline Greenan; Richard Kennedy

doi:10.1016/j.bmcl.2013.03.035

Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors

Meilan Huang^*, Zhuo Li, Dawei Li, Steven Walker, Caroline Greenan, Richard Kennedy

^*Corresponding author for this work

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

2 Citations (Scopus)

Abstract

We identified nine small-molecule hit compounds of Heat shock 70 kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5.

Original language	English
Pages (from-to)	3044-3050
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	23
Issue number	10
Early online date	16 Mar 2013
DOIs	https://doi.org/10.1016/j.bmcl.2013.03.035
Publication status	Published - 15 May 2013

Keywords

Peptide substrate
Apoptosis
HEAT-SHOCK-PROTEIN
HSP70
HSP90
CHAPERONE DNAK
Cancer
In silico screening
INDUCED APOPTOSIS
SUBSTRATE-BINDING
IDENTIFICATION
HSP70 inhibitors
HEAT-SHOCK-PROTEIN-70
SPECIFICITY
MODULATORS

UN SDGs

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

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10.1016/j.bmcl.2013.03.035Licence: Unspecified

Cite this

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title = "Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors",

abstract = "We identified nine small-molecule hit compounds of Heat shock 70 kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5. ",

keywords = "Peptide substrate, Apoptosis, HEAT-SHOCK-PROTEIN, HSP70, HSP90, CHAPERONE DNAK, Cancer, In silico screening, INDUCED APOPTOSIS, SUBSTRATE-BINDING, IDENTIFICATION, HSP70 inhibitors, HEAT-SHOCK-PROTEIN-70, SPECIFICITY, MODULATORS",

author = "Meilan Huang and Zhuo Li and Dawei Li and Steven Walker and Caroline Greenan and Richard Kennedy",

year = "2013",

month = may,

day = "15",

doi = "10.1016/j.bmcl.2013.03.035",

language = "English",

volume = "23",

pages = "3044--3050",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "10",

}

TY - JOUR

T1 - Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors

AU - Huang, Meilan

AU - Li, Zhuo

AU - Li, Dawei

AU - Walker, Steven

AU - Greenan, Caroline

AU - Kennedy, Richard

PY - 2013/5/15

Y1 - 2013/5/15

N2 - We identified nine small-molecule hit compounds of Heat shock 70 kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5.

AB - We identified nine small-molecule hit compounds of Heat shock 70 kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5.

KW - Peptide substrate

KW - Apoptosis

KW - HEAT-SHOCK-PROTEIN

KW - HSP70

KW - HSP90

KW - CHAPERONE DNAK

KW - Cancer

KW - In silico screening

KW - INDUCED APOPTOSIS

KW - SUBSTRATE-BINDING

KW - IDENTIFICATION

KW - HSP70 inhibitors

KW - HEAT-SHOCK-PROTEIN-70

KW - SPECIFICITY

KW - MODULATORS

U2 - 10.1016/j.bmcl.2013.03.035

DO - 10.1016/j.bmcl.2013.03.035

M3 - Article

VL - 23

SP - 3044

EP - 3050

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 10

ER -

Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors

Abstract

Keywords

UN SDGs

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