Discovery of (E)-5-(benzylideneamino)-1H-benzo[d]imidazol-2(3H)-one derivatives as inhibitors for PTK6

Hyun Jae Shim; Hye Ran Yang; Han Ie Kim; Shin Ae Kang; Kyoung Tai No; Young Hoon Jung; Seung Taek Lee

doi:10.1016/j.bmcl.2014.08.036

Discovery of (E)-5-(benzylideneamino)-1H-benzo[d]imidazol-2(3H)-one derivatives as inhibitors for PTK6

Hyun Jae Shim, Hye Ran Yang, Han Ie Kim, Shin Ae Kang, Kyoung Tai No, Young Hoon Jung, Seung Taek Lee

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

12 Citations (Scopus)

Abstract

A lead compound 1, which inhibits the catalytic activity of PTK6, was selected from a chemical library. Derivatives of compound 1 were synthesized and analyzed for inhibitory activity against PTK6 in vitro and at the cellular level. Selected compounds were analyzed for cytotoxicity in human foreskin fibroblasts using MTT assays and for selectivity towards PTK members in HEK 293 cells. Compounds 20 (in vitro IC₅₀= 0.12 μM) and 21 (in vitro IC₅₀= 0.52 μM) showed little cytotoxicity, excellent inhibition of PTK6 in vitro and at the cellular level, and selectivity for PTK6. Compounds 20 and 21 inhibited phosphorylation of specific PTK6 substrates in HEK293 cells. Thus, we have identified novel PTK6 inhibitors that may be used as treatments for PTK6-positive carcinomas, including breast cancer.

Original language	English
Pages (from-to)	4659-4663
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2014.08.036
Publication status	Published - 2014 Oct 1

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation Grant funded by the Government of Republic of Korea (MSIP) (No. 2013R1A2A2A01013884 ).

Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.

All Science Journal Classification (ASJC) codes

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

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title = "Discovery of (E)-5-(benzylideneamino)-1H-benzo[d]imidazol-2(3H)-one derivatives as inhibitors for PTK6",

abstract = "A lead compound 1, which inhibits the catalytic activity of PTK6, was selected from a chemical library. Derivatives of compound 1 were synthesized and analyzed for inhibitory activity against PTK6 in vitro and at the cellular level. Selected compounds were analyzed for cytotoxicity in human foreskin fibroblasts using MTT assays and for selectivity towards PTK members in HEK 293 cells. Compounds 20 (in vitro IC50= 0.12 μM) and 21 (in vitro IC50= 0.52 μM) showed little cytotoxicity, excellent inhibition of PTK6 in vitro and at the cellular level, and selectivity for PTK6. Compounds 20 and 21 inhibited phosphorylation of specific PTK6 substrates in HEK293 cells. Thus, we have identified novel PTK6 inhibitors that may be used as treatments for PTK6-positive carcinomas, including breast cancer.",

author = "Shim, {Hyun Jae} and Yang, {Hye Ran} and Kim, {Han Ie} and Kang, {Shin Ae} and No, {Kyoung Tai} and Jung, {Young Hoon} and Lee, {Seung Taek}",

note = "Funding Information: This work was supported by a National Research Foundation Grant funded by the Government of Republic of Korea (MSIP) (No. 2013R1A2A2A01013884 ). Publisher Copyright: {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",

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doi = "10.1016/j.bmcl.2014.08.036",

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AU - Shim, Hyun Jae

AU - Yang, Hye Ran

AU - Kim, Han Ie

AU - Kang, Shin Ae

AU - No, Kyoung Tai

AU - Jung, Young Hoon

AU - Lee, Seung Taek

N1 - Funding Information: This work was supported by a National Research Foundation Grant funded by the Government of Republic of Korea (MSIP) (No. 2013R1A2A2A01013884 ). Publisher Copyright: © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/10/1

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N2 - A lead compound 1, which inhibits the catalytic activity of PTK6, was selected from a chemical library. Derivatives of compound 1 were synthesized and analyzed for inhibitory activity against PTK6 in vitro and at the cellular level. Selected compounds were analyzed for cytotoxicity in human foreskin fibroblasts using MTT assays and for selectivity towards PTK members in HEK 293 cells. Compounds 20 (in vitro IC50= 0.12 μM) and 21 (in vitro IC50= 0.52 μM) showed little cytotoxicity, excellent inhibition of PTK6 in vitro and at the cellular level, and selectivity for PTK6. Compounds 20 and 21 inhibited phosphorylation of specific PTK6 substrates in HEK293 cells. Thus, we have identified novel PTK6 inhibitors that may be used as treatments for PTK6-positive carcinomas, including breast cancer.

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Discovery of (E)-5-(benzylideneamino)-1H-benzo[d]imidazol-2(3H)-one derivatives as inhibitors for PTK6

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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