topoisomerase i inhibitors


Summary: Compounds that inhibit the activity of DNA TOPOISOMERASE I.

Top Publications

  1. Pommier Y. DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition. Chem Rev. 2009;109:2894-902 pubmed publisher
  2. Liu L. DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem. 1989;58:351-75 pubmed
  3. Chakraborty A, Majumder H. Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochem Biophys Res Commun. 1988;152:605-11 pubmed
    ..The inhibition reported here concerning a type I DNA topoisomerase demonstrates at least one possible mode of action of these antileishmanial drugs...
  4. Verma R, Hansch C. Camptothecins: a SAR/QSAR study. Chem Rev. 2009;109:213-35 pubmed publisher
  5. Agatsuma T. Development of New ADC Technology with Topoisomerase I Inhibitor. Yakugaku Zasshi. 2017;137:545-550 pubmed publisher
    ..These results suggest that DS-8201a may be efficacious in a broader population of HER2-positive cancer patients and also confirm the importance of this new class of novel topoisomerase I inhibitor-based ADC technology. ..
  6. Nukuzuma S, Nukuzuma C, Kameoka M, Sugiura S, Nakamichi K, Tasaki T, et al. CPT11 prevents virus replication in JCI cells persistently infected with JC polyomavirus. Microbiol Immunol. 2017;61:232-238 pubmed publisher
    ..It has been demonstrated that the topoisomerase I inhibitors topotecan and ?-lapachone have inhibitory effects on JCPyV replication in IMR-32 cells...
  7. Takegawa N, Nonagase Y, Yonesaka K, Sakai K, Maenishi O, Ogitani Y, et al. DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance. Int J Cancer. 2017;141:1682-1689 pubmed publisher
    ..Notably, N87-TDMR xenograft tumor growth was prevented by DS-8201a. In conclusion, the efficacy of DS-8201a as a treatment for patients with T-DM1-resistant breast or gastric cancer merits investigation. ..
  8. Ranjan N, Story S, Fulcrand G, Leng F, Ahmad M, King A, et al. Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst 33258 Derived Mono- and Bisbenzimidazoles. J Med Chem. 2017;60:4904-4922 pubmed publisher
    ..2-23.4 °C), and cytotoxicity studies show similar variation dependent upon the side chain length. Modeling studies suggest critical interactions between the inhibitor side chain and amino acids of the active site of DNA topoisomerase I. ..
  9. Allison S, Sadiq M, Baronou E, Cooper P, Dunnill C, Georgopoulos N, et al. Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands. Cancer Lett. 2017;403:98-107 pubmed publisher
    ..Thus, Ag8 targets multiple pathways of importance in cancer biology, is less active against non-cancer cells and shows activity in vivo in a loco-regional setting. ..

More Information


  1. Luo P, Yu Q, Liu S, Xia W, Fang Y, An L, et al. Diterpenoids with diverse scaffolds from Vitex trifolia as potential topoisomerase I inhibitor. Fitoterapia. 2017;120:108-116 pubmed publisher
    ..Compounds 8 and 11 exhibited equipotent Top1 inhibitory activity to the positive control, camptothecin (CPT), at 100?M. Compounds 8, 9, 16, and 27 showed moderate cytotoxicity at low micromolar concentrations. ..
  2. Koosha F, Neshasteh Riz A, Takavar A, Eyvazzadeh N, Mazaheri Z, Eynali S, et al. The combination of A-966492 and Topotecan for effective radiosensitization on glioblastoma spheroids. Biochem Biophys Res Commun. 2017;491:1092-1097 pubmed publisher
    ..A-966492 combined with TPT as a topoisomerase I inhibitor had additive radio-sensitizing effects. As a result, applying PARP and topoisomerase I inhibitors can be a suitable strategy for improving radiotherapy in clinics.
  3. D ARPA P, Beardmore C, Liu L. Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res. 1990;50:6919-24 pubmed
    ..This antagonistic effect between topoisomerase I and II poisons could be explained by the strong inhibitory effect of camptothecin on RNA transcription. ..
  4. Elsayed M, Su Y, Wang P, Sethi T, Agama K, Ravji A, et al. Design and Synthesis of Chlorinated and Fluorinated 7-Azaindenoisoquinolines as Potent Cytotoxic Anticancer Agents That Inhibit Topoisomerase I. J Med Chem. 2017;60:5364-5376 pubmed publisher
    ..630 ?M) range. Compounds 16b and 17b are the most potent in human cancer cell cultures with MGM GI50 values of 0.063 and 0.033 ?M, respectively. Possible binding modes to Top1 and TDP1were investigated by molecular modeling. ..
  5. Bremer J, Skinner J, Granato M. A small molecule screen identifies in vivo modulators of peripheral nerve regeneration in zebrafish. PLoS ONE. 2017;12:e0178854 pubmed publisher
    ..Thus, we established a technically simple assay to rapidly identify valuable entry points into pathways critical for vertebrate peripheral nerve regeneration. ..
  6. Rishi P, Sharma T, Sharma M, Maitray A, Dhami A, Aggarwal V, et al. Intra-arterial chemotherapy for retinoblastoma: Two-year results from tertiary eye-care center in India. Indian J Ophthalmol. 2017;65:311-315 pubmed publisher
    ..IAC is an effective therapy for globe preservation in eyes with intraocular RB, in the setting of a developing country like India. Larger studies with longer follow-up are required to validate these results. ..
  7. Chowdhury S, Kumar A, Godinho J, De Macedo Silva S, Zuma A, Saha S, et al. Voacamine alters Leishmania ultrastructure and kills parasite by poisoning unusual bi-subunit topoisomerase IB. Biochem Pharmacol. 2017;138:19-30 pubmed publisher
    ..The findings cumulatively provide a strong evidence that voacamine can be a promising drug candidate against trypanosomatid infections. ..
  8. He K, Zhang C, Duan Y, Huang G, Yang C, Lu X, et al. New chlorinated xanthone and anthraquinone produced by a mangrove-derived fungus Penicillium citrinum HL-5126. J Antibiot (Tokyo). 2017;70:823-827 pubmed publisher
    ..All compounds were evaluated for their antibacterial and topoisomerase I inhibitory activities. Compound 2 exhibited antibacterial activity against Vibrio parahaemolyticus with an MIC value of 10??m. ..
  9. Wang P, Elsayed M, Plescia C, Ravji A, Redon C, Kiselev E, et al. Synthesis and Biological Evaluation of the First Triple Inhibitors of Human Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), and Tyrosyl-DNA Phosphodiesterase 2 (Tdp2). J Med Chem. 2017;60:3275-3288 pubmed publisher
    ..The monitoring of DNA damage by ?-H2AX foci formation in human PBMCs (lymphocytes) and acute lymphoblastic leukemia CCRF-CEM cells documented significantly more DNA damage in the cancer cells vs normal cells. ..
  10. Lafayette E, de Almeida S, Cavalcanti Santos R, de Oliveira J, Amorim C, da Silva R, et al. Synthesis of novel indole derivatives as promising DNA-binding agents and evaluation of antitumor and antitopoisomerase I activities. Eur J Med Chem. 2017;136:511-522 pubmed publisher
    ..Moreover, it was highlighted that basic side chains, such as thiazolidines and imidazolidines, and free amino group, are relevant for design of promising antitumor and DNA binding compounds. ..