Tags

Type your tag names separated by a space and hit enter

Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I.
Cancer Res. 1999 Sep 01; 59(17):4271-5.CR

Abstract

J-107088 [6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carb azo le-5,7(6H)-dione] is a new derivative of NB-506, an indolocarbazole antitumor agent. J-107088 induced single-strand DNA cleavage only in the presence of topoisomerase I (top1) more effectively than NB-506 or camptothecin. The preferable sequences of the DNA cleaved by J-107088 were C/T / G as in the case of NB-506. This base-preference of J-107088 in top1-mediated cleavage was different from that of camptothecin, which was T / G/A. top1 poisons stabilize the complex between DNA and top1 (cleavable complex). This cleavable complex is released on addition of a high concentration of monovalent cation or removal of top1 poisons. The complex induced by J-107088 was quite stable; it was scarcely released on the addition of NaCl or dilution of J-107088, contrary to the case with camptothecin and NB-506. J-107088-inducing complexes were also stable in cultured cells, when the compound was added to the culture medium. These unique in vitro activities of J-107088 on top1 that differed from those of camptothecin and NB-506 may be relevant to its more potent in vivo antitumor efficacy in a human tumor xenographted nude mouse model.

Authors+Show Affiliations

Banyu Tsukuba Research Institute and Merck Research Laboratories, Japan.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 available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10485471

Citation

Yoshinari, T, et al. "Mode of Action of a New Indolocarbazole Anticancer Agent, J-107088, Targeting Topoisomerase I." Cancer Research, vol. 59, no. 17, 1999, pp. 4271-5.
Yoshinari T, Ohkubo M, Fukasawa K, et al. Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I. Cancer Res. 1999;59(17):4271-5.
Yoshinari, T., Ohkubo, M., Fukasawa, K., Egashira, S., Hara, Y., Matsumoto, M., Nakai, K., Arakawa, H., Morishima, H., & Nishimura, S. (1999). Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I. Cancer Research, 59(17), 4271-5.
Yoshinari T, et al. Mode of Action of a New Indolocarbazole Anticancer Agent, J-107088, Targeting Topoisomerase I. Cancer Res. 1999 Sep 1;59(17):4271-5. PubMed PMID: 10485471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I. AU - Yoshinari,T, AU - Ohkubo,M, AU - Fukasawa,K, AU - Egashira,S, AU - Hara,Y, AU - Matsumoto,M, AU - Nakai,K, AU - Arakawa,H, AU - Morishima,H, AU - Nishimura,S, PY - 1999/9/15/pubmed PY - 1999/9/15/medline PY - 1999/9/15/entrez SP - 4271 EP - 5 JF - Cancer research JO - Cancer Res VL - 59 IS - 17 N2 - J-107088 [6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carb azo le-5,7(6H)-dione] is a new derivative of NB-506, an indolocarbazole antitumor agent. J-107088 induced single-strand DNA cleavage only in the presence of topoisomerase I (top1) more effectively than NB-506 or camptothecin. The preferable sequences of the DNA cleaved by J-107088 were C/T / G as in the case of NB-506. This base-preference of J-107088 in top1-mediated cleavage was different from that of camptothecin, which was T / G/A. top1 poisons stabilize the complex between DNA and top1 (cleavable complex). This cleavable complex is released on addition of a high concentration of monovalent cation or removal of top1 poisons. The complex induced by J-107088 was quite stable; it was scarcely released on the addition of NaCl or dilution of J-107088, contrary to the case with camptothecin and NB-506. J-107088-inducing complexes were also stable in cultured cells, when the compound was added to the culture medium. These unique in vitro activities of J-107088 on top1 that differed from those of camptothecin and NB-506 may be relevant to its more potent in vivo antitumor efficacy in a human tumor xenographted nude mouse model. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/10485471/Mode_of_action_of_a_new_indolocarbazole_anticancer_agent_J_107088_targeting_topoisomerase_I_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10485471 DB - PRIME DP - Unbound Medicine ER -