Add time:09/03/2019 Source:sciencedirect.com
A new derivative of 1-phenyl-3-methyl-5-pyrazolone, 4,4-dichloro-1-(2,4-dichlorophenyl)-3-methyl-5-pyrazolone, named TELIN, was chemically synthesized and identified as a potent inhibitor of human telomerase in the cell-free telomeric repeat amplification protocol. TELIN inhibited telomerase activity at submicromolar level with IC50 of ∼0.3 μM. Kinetic studies revealed that TELIN does not bind to DNA but to telomerase protein, and the mode of inhibition by this substance was competitive–noncompetitive mixed-type with respect to the TS primer, whereas it was uncompetitive or noncompetitive–uncompetitive mixed-type with respect to the three deoxyribonucleosides. These results demonstrate that TELIN is a specific potent catalytic blocker of telomerase, and is considered to be a valuable substance for medical treatment of cancer and related diseases.
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