5-Aryl-4-(5-substituted-2,4-dihydroxyphenyl)-1,2,3-thiadiazoles as inhibitors of Hsp90 chaperone

Inga Cikotiene; Egidijus Kazlauskas; Jurgita Matuliene; Vilma Michailoviene; Jolanta Torresan; Jelena Jachno; Daumantas Matulis

doi:10.1016/j.bmcl.2009.01.003

5-Aryl-4-(5-substituted-2,4-dihydroxyphenyl)-1,2,3-thiadiazoles as inhibitors of Hsp90 chaperone

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1089-92. doi: 10.1016/j.bmcl.2009.01.003. Epub 2009 Jan 9.

Authors

Inga Cikotiene¹, Egidijus Kazlauskas, Jurgita Matuliene, Vilma Michailoviene, Jolanta Torresan, Jelena Jachno, Daumantas Matulis

Affiliation

¹ Laboratory of Biothermodynamics and Drug Design, Insitute of Biotechnology, Graiciuno 8, Vilnius LT-02241, Lithuania.

PMID: 19168355
DOI: 10.1016/j.bmcl.2009.01.003

Abstract

A series of 5-aryl-4-(5-substituted-2,4-dihydroxyphenyl)-1,2,3-thiadiazoles were synthesized and their binding to several constructs of human Hsp90 chaperone measured by isothermal titration calorimetry (ITC). The most potent compound bound Hsp90 with the dissociation constant of about 5 nM.

MeSH terms

Combinatorial Chemistry Techniques
Drug Screening Assays, Antitumor
HSP90 Heat-Shock Proteins / antagonists & inhibitors*
Humans
Molecular Chaperones / antagonists & inhibitors*
Molecular Structure
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Thiadiazoles / chemical synthesis*
Thiadiazoles / chemistry
Thiadiazoles / pharmacology*

Substances

HSP90 Heat-Shock Proteins
Molecular Chaperones
Pyrazoles
Thiadiazoles