Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)

Nicole Mayer; Martina Schweiger; Elisabeth Fuchs; Anna K. Migglautsch; Carina Doler; Gernot F. Grabner; Matthias Romauch,; Michaela Christina Melcher; Rudolf Zechner; Robert Zimmermann; Rolf Breinbauer

doi:10.1016/j.bmc.2020.115610

Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)

Nicole Mayer, Martina Schweiger, Elisabeth Fuchs, Anna K. Migglautsch, Carina Doler, Gernot F. Grabner, Matthias Romauch,, Michaela Christina Melcher, Rudolf Zechner, Robert Zimmermann, Rolf Breinbauer^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Publikation: Beitrag in einer Fachzeitschrift › Artikel › Begutachtung

Abstract

High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.

Originalsprache	englisch
Aufsatznummer	115610
Fachzeitschrift	Bioorganic and Medicinal Chemistry
Jahrgang	28
Ausgabenummer	16
DOIs	https://doi.org/10.1016/j.bmc.2020.115610
Publikationsstatus	Veröffentlicht - 15 Aug. 2020

ASJC Scopus subject areas

Biochemie
Molekularmedizin
Molekularbiologie
Pharmazeutische Wissenschaften
Wirkstoffforschung
Klinische Biochemie
Organische Chemie

Fields of Expertise

Human- & Biotechnology

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

Zugriff auf Dokument

10.1016/j.bmc.2020.115610

Andere Dateien und Links

http://www.scopus.com/inward/record.url?scp=85087693804&partnerID=8YFLogxK

Atglistatin - Präklinische Entwicklung von ATGL-Inhibitoren
Breinbauer, R.
1/05/17 → 30/04/21
Projekt: Forschungsprojekt
FWF-Inhibitoren für hATGL - Entwicklung von niedermolekularen Inhibitoren der humanen Adiposen Triglyzeridlipase
Breinbauer, R.
1/08/15 → 31/07/19
Projekt: Forschungsprojekt

Dieses zitieren

Mayer, N., Schweiger, M., Fuchs, E., Migglautsch, A. K., Doler, C., Grabner, G. F., Romauch, M., Melcher, M. C., Zechner, R., Zimmermann, R., & Breinbauer, R. (2020). Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL). Bioorganic and Medicinal Chemistry, 28(16), Artikel 115610. https://doi.org/10.1016/j.bmc.2020.115610

Mayer, N, Schweiger, M, Fuchs, E, Migglautsch, AK, Doler, C, Grabner, GF, Romauch, M, Melcher, MC, Zechner, R, Zimmermann, R & Breinbauer, R 2020, 'Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)', Bioorganic and Medicinal Chemistry, Jg. 28, Nr. 16, 115610. https://doi.org/10.1016/j.bmc.2020.115610

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title = "Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)",

abstract = "High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.",

keywords = "Atglistatin, Lipolysis, NAFLD, PNPLA2, Small molecule inhibitor",

author = "Nicole Mayer and Martina Schweiger and Elisabeth Fuchs and Migglautsch, {Anna K.} and Carina Doler and Grabner, {Gernot F.} and Matthias Romauch, and Melcher, {Michaela Christina} and Rudolf Zechner and Robert Zimmermann and Rolf Breinbauer",

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doi = "10.1016/j.bmc.2020.115610",

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T1 - Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)

AU - Mayer, Nicole

AU - Schweiger, Martina

AU - Fuchs, Elisabeth

AU - Migglautsch, Anna K.

AU - Doler, Carina

AU - Grabner, Gernot F.

AU - Romauch,, Matthias

AU - Melcher, Michaela Christina

AU - Zechner, Rudolf

AU - Zimmermann, Robert

AU - Breinbauer, Rolf

PY - 2020/8/15

Y1 - 2020/8/15

N2 - High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.

AB - High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.

KW - Atglistatin

KW - Lipolysis

KW - NAFLD

KW - PNPLA2

KW - Small molecule inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85087693804&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2020.115610

DO - 10.1016/j.bmc.2020.115610

M3 - Article

AN - SCOPUS:85087693804

SN - 0968-0896

VL - 28

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 16

M1 - 115610

ER -

Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)

Abstract

ASJC Scopus subject areas

Fields of Expertise

UN SDGs

Zugriff auf Dokument

Andere Dateien und Links

Fingerprint

Projekte

Atglistatin - Präklinische Entwicklung von ATGL-Inhibitoren

FWF-Inhibitoren für hATGL - Entwicklung von niedermolekularen Inhibitoren der humanen Adiposen Triglyzeridlipase

Dieses zitieren