Research output: Contribution to journal › Article › peer-review
The Influence of TDP1 Inhibitor Usnic Acid Derivative OL9-116 on the Effects of Topotecan in Human Cells. / Kornienko, Tatyana E.; Chepanova, Arina A.; Kolobenko, Maria V. et al.
In: Current issues in molecular biology, Vol. 48, No. 4, 428, 21.04.2026.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - The Influence of TDP1 Inhibitor Usnic Acid Derivative OL9-116 on the Effects of Topotecan in Human Cells
AU - Kornienko, Tatyana E.
AU - Chepanova, Arina A.
AU - Kolobenko, Maria V.
AU - Chernyshova, Irina A.
AU - Zakharenko, Alexandra L.
AU - Venzel, Artur S.
AU - Dyrkheeva, Nadezhda S.
AU - Markov, Andrey V.
AU - Anarbaev, Rashid O.
AU - Naumenko, Konstantin N.
AU - Luzina, Olga A.
AU - Salakhutdinov, Nariman F.
AU - Ivanisenko, Vladimir A.
AU - Lavrik, Olga I.
N1 - The Influence of TDP1 Inhibitor Usnic Acid Derivative OL9-116 on the Effects of Topotecan in Human Cells / T. E. Kornienko, A. A. Chepanova, M. V. Kolobenko [et al.] // Current Issues in Molecular Biology. – 2026. – Vol. 48, No. 4. – P. 428. – DOI 10.3390/cimb48040428. – EDN DHJCIY. This study was funded by Russian Science Foundation (grant no. 25-24-00247).
PY - 2026/4/21
Y1 - 2026/4/21
N2 - Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a key enzyme for the repair of stalled topoi-somerase 1 (TOP1)-DNA complexes. We have previously developed a TDP1 inhibitor, compound OL9-116, which is capable of enhancing the action of the anticancer drug topotecan (TPC), a TOP1 poison, in vitro and in vivo. In this study, the inhibition mode of OL9-116 (uncompetitive) was investigated. We have shown that N-terminal domain of TDP1, which is important for the cell function of TDP1 but is not involved in catalysis directly, reduced the inhibitory potency of OL9-116 probably by influencing the conformation of the enzyme. OL9-116 did not reduce cell viability and did not affect mitochondrial membrane potential. OL9-116 enhanced the cytotoxic/antiproliferative effect of TPC on the panel of tumor cells. This effect was not observed on nontumor cells or TDP1-deficient cells. OL9-116 and TPC had different effects on TDP1 and TOP1 gene expression detected by PCR depending on the cell type and the presence of functional TDP1. The direct relation between the effects of the compounds on the gene expression and cell survival was not found. The obtained data indicated a synergistic effect of OL9-116 and TPC, which appeared to be mediated by TDP1 inhibition rather than by an effect on TDP1 gene expression.
AB - Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a key enzyme for the repair of stalled topoi-somerase 1 (TOP1)-DNA complexes. We have previously developed a TDP1 inhibitor, compound OL9-116, which is capable of enhancing the action of the anticancer drug topotecan (TPC), a TOP1 poison, in vitro and in vivo. In this study, the inhibition mode of OL9-116 (uncompetitive) was investigated. We have shown that N-terminal domain of TDP1, which is important for the cell function of TDP1 but is not involved in catalysis directly, reduced the inhibitory potency of OL9-116 probably by influencing the conformation of the enzyme. OL9-116 did not reduce cell viability and did not affect mitochondrial membrane potential. OL9-116 enhanced the cytotoxic/antiproliferative effect of TPC on the panel of tumor cells. This effect was not observed on nontumor cells or TDP1-deficient cells. OL9-116 and TPC had different effects on TDP1 and TOP1 gene expression detected by PCR depending on the cell type and the presence of functional TDP1. The direct relation between the effects of the compounds on the gene expression and cell survival was not found. The obtained data indicated a synergistic effect of OL9-116 and TPC, which appeared to be mediated by TDP1 inhibition rather than by an effect on TDP1 gene expression.
KW - DNA repair
KW - TDP1 knockout
KW - Tyrosyl-DNA phosphodiesterase 1 inhibitor
KW - topotecan
KW - usnic acid derivative
KW - Репарация ДНК
KW - ингибитор тирозил-ДНК-фосфодиэстеразы 1
KW - топотекан
KW - нокаут TDP1
KW - производное усниновой кислоты
UR - https://www.mendeley.com/catalogue/9e6d77d6-cd8d-3eeb-bb0d-0218a0af0455/
UR - https://www.scopus.com/pages/publications/105037035068
UR - https://www.elibrary.ru/item.asp?id=90978113
U2 - 10.3390/cimb48040428
DO - 10.3390/cimb48040428
M3 - Article
VL - 48
JO - Current issues in molecular biology
JF - Current issues in molecular biology
SN - 1467-3037
IS - 4
M1 - 428
ER -
ID: 85171006