TY  - JOUR
AU  - Baranauskiene, L.
AU  - Hilvo, M.
AU  - Matuliene, J.
AU  - Golovenko, D.
AU  - Manakova, E.
AU  - Dudutiene, V.
AU  - Michailoviene, V.
AU  - Torresan, J.
AU  - Jachno, J.
AU  - Parkkila, S.
AU  - Maresca, A.
AU  - Supuran, C.
AU  - Grazulis, S.
AU  - Matulis, D.
AU  - DESY
TI  - Inhibition and binding studies of carbonic anhydrase isozymes I, II and IX with benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides
JO  - Journal of enzyme inhibition and medicinal chemistry
VL  - 25
SN  - 1475-6374
CY  - London
PB  - Informa Healthcare
M1  - PHPPUBDB-24676
SP  - 863-870
PY  - 2010
AB  - The binding and inhibition strength of a series of benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides were determined for recombinant human carbonic anhydrase isoforms I, II, and IX. The inhibition strength was determined by a stop-flow method to measure carbon dioxide hydration. Inhibitor-enzyme binding was determined by two biophysical techniques-isothermal titration calorimetry and thermal shift assay. The co-crystal structure was determined by X-ray crystallography. Comparing the results obtained using three different inhibition and binding methods increased the accuracy of compound affinity ranking and the ability to determine compound inhibitory specificity towards a particular carbonic anhydrase isoform. In most cases, all three methods yielded the same results despite using very different approaches to measure the binding and inhibition reactions. Some of the compounds studied are submicromolar inhibitors of the isoform IX, a prominent cancer target.
KW  - Algorithms
KW  - Antigens, Neoplasm: genetics
KW  - Antigens, Neoplasm: metabolism
KW  - Antineoplastic Agents: chemistry
KW  - Antineoplastic Agents: metabolism
KW  - Antineoplastic Agents: pharmacology
KW  - Benzimidazoles: chemistry
KW  - Benzimidazoles: metabolism
KW  - Benzimidazoles: pharmacology
KW  - Calorimetry: methods
KW  - Carbonic Anhydrase I: antagonists & inhibitors
KW  - Carbonic Anhydrase I: genetics
KW  - Carbonic Anhydrase I: metabolism
KW  - Carbonic Anhydrase II: antagonists & inhibitors
KW  - Carbonic Anhydrase II: chemistry
KW  - Carbonic Anhydrase II: genetics
KW  - Carbonic Anhydrase II: metabolism
KW  - Carbonic Anhydrase Inhibitors: chemistry
KW  - Carbonic Anhydrase Inhibitors: metabolism
KW  - Carbonic Anhydrase Inhibitors: pharmacology
KW  - Carbonic Anhydrases: genetics
KW  - Carbonic Anhydrases: metabolism
KW  - Catalytic Domain: drug effects
KW  - Crystallography, X-Ray
KW  - Humans
KW  - Kinetics
KW  - Ligands
KW  - Molecular Conformation
KW  - Recombinant Proteins: antagonists & inhibitors
KW  - Recombinant Proteins: chemistry
KW  - Recombinant Proteins: metabolism
KW  - Sulfonamides: chemistry
KW  - Sulfonamides: metabolism
KW  - Sulfonamides: pharmacology
KW  - Thiadiazoles: chemistry
KW  - Thiadiazoles: metabolism
KW  - Thiadiazoles: pharmacology
KW  - Antigens, Neoplasm (NLM Chemicals)
KW  - Antineoplastic Agents (NLM Chemicals)
KW  - Benzimidazoles (NLM Chemicals)
KW  - Carbonic Anhydrase Inhibitors (NLM Chemicals)
KW  - Ligands (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - Sulfonamides (NLM Chemicals)
KW  - Thiadiazoles (NLM Chemicals)
KW  - Carbonic Anhydrase I (NLM Chemicals)
KW  - Carbonic Anhydrase II (NLM Chemicals)
KW  - CA9 protein, human (NLM Chemicals)
KW  - Carbonic Anhydrases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:20166809
UR  - <Go to ISI:>//WOS:000283939300016
DO  - DOI:10.3109/14756360903571685
UR  - https://bib-pubdb1.desy.de/record/140090
ER  -