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Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968.
. 2008 Jul; 7(7):2051-9.

Abstract

ST1968 is a novel hydrophilic camptothecin (CPT) derivative of the 7-oxyiminomethyl series. Because ST1968 retained ability to form remarkably stable cleavable complexes, this study was done to investigate its preclinical profile of antitumor activity in a large panel of human tumor models, including irinotecan-resistant tumors. Although less potent than SN38 in vitro, i.v. administered ST1968 caused a marked tumor inhibition, superior to that of irinotecan, in most tested models. ST1968 exhibited an impressive activity against several tumors including models of ovarian and colon carcinoma in which a high rate of cures was observed. In the most responsive tumors, complete and persistent tumor regressions were achieved even with low suboptimal doses. Even tumors derived from intrinsically resistant cells exhibited a significant responsiveness. Histologic analysis of treated tumors supports a contribution of both proapoptotic and antiangiogenic effects to ST1968 antitumor efficacy. A study done in yeast cells transformed with CPT-resistant mutant forms of topoisomerase I documented that, in contrast to other tested CPT, ST1968 was active against yeasts expressing the mutant K720E enzyme. Based on its outstanding efficacy superior to that of irinotecan and of its good therapeutic index, ST1968 has been selected for clinical development.

Authors+Show Affiliations

Sigma-Tau, Pomezia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18645015

Citation

Pisano, Claudio, et al. "Preclinical Profile of Antitumor Activity of a Novel Hydrophilic Camptothecin, ST1968." Molecular Cancer Therapeutics, vol. 7, no. 7, 2008, pp. 2051-9.
Pisano C, De Cesare M, Beretta GL, et al. Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968. Mol Cancer Ther. 2008;7(7):2051-9.
Pisano, C., De Cesare, M., Beretta, G. L., Zuco, V., Pratesi, G., Penco, S., Vesci, L., Foderà, R., Ferrara, F. F., Guglielmi, M. B., Carminati, P., Dallavalle, S., Morini, G., Merlini, L., Orlandi, A., & Zunino, F. (2008). Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968. Molecular Cancer Therapeutics, 7(7), 2051-9. https://doi.org/10.1158/1535-7163.MCT-08-0266
Pisano C, et al. Preclinical Profile of Antitumor Activity of a Novel Hydrophilic Camptothecin, ST1968. Mol Cancer Ther. 2008;7(7):2051-9. PubMed PMID: 18645015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968. AU - Pisano,Claudio, AU - De Cesare,Michelandrea, AU - Beretta,Giovanni Luca, AU - Zuco,Valentina, AU - Pratesi,Graziella, AU - Penco,Sergio, AU - Vesci,Loredana, AU - Foderà,Rosanna, AU - Ferrara,Fabiana Fosca, AU - Guglielmi,Mario Berardino, AU - Carminati,Paolo, AU - Dallavalle,Sabrina, AU - Morini,Gabriella, AU - Merlini,Lucio, AU - Orlandi,Augusto, AU - Zunino,Franco, PY - 2008/7/23/pubmed PY - 2008/9/9/medline PY - 2008/7/23/entrez SP - 2051 EP - 9 JF - Molecular cancer therapeutics JO - Mol. Cancer Ther. VL - 7 IS - 7 N2 - ST1968 is a novel hydrophilic camptothecin (CPT) derivative of the 7-oxyiminomethyl series. Because ST1968 retained ability to form remarkably stable cleavable complexes, this study was done to investigate its preclinical profile of antitumor activity in a large panel of human tumor models, including irinotecan-resistant tumors. Although less potent than SN38 in vitro, i.v. administered ST1968 caused a marked tumor inhibition, superior to that of irinotecan, in most tested models. ST1968 exhibited an impressive activity against several tumors including models of ovarian and colon carcinoma in which a high rate of cures was observed. In the most responsive tumors, complete and persistent tumor regressions were achieved even with low suboptimal doses. Even tumors derived from intrinsically resistant cells exhibited a significant responsiveness. Histologic analysis of treated tumors supports a contribution of both proapoptotic and antiangiogenic effects to ST1968 antitumor efficacy. A study done in yeast cells transformed with CPT-resistant mutant forms of topoisomerase I documented that, in contrast to other tested CPT, ST1968 was active against yeasts expressing the mutant K720E enzyme. Based on its outstanding efficacy superior to that of irinotecan and of its good therapeutic index, ST1968 has been selected for clinical development. SN - 1535-7163 UR - https://www.unboundmedicine.com/medline/citation/18645015/Preclinical_profile_of_antitumor_activity_of_a_novel_hydrophilic_camptothecin_ST1968_ L2 - http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18645015 DB - PRIME DP - Unbound Medicine ER -