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Chemical Compound Review

AC1NUHAR     (2E,4E)-N-[[2-(1,2- dihydroxyethyl)-4,5...

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Disease relevance of KRN5500

  • KRN5500: a novel therapeutic agent with in vitro activity against human B-cell chronic lymphocytic leukemia cells mediates cytotoxicity via the intrinsic pathway of apoptosis [1].
  • A Phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetic behavior of KRN5500 given as a 1-h i.v. infusion for 5 consecutive days every 3 weeks [2].
  • In the chemotherapy of experimental hepatic metastasis induced by intrasplenic injection of COL-1 cells, KRN5500 at 12 mg/kg per day was administered i.v. three times at 4-day intervals [3].
  • METHODS: We investigated the effects of combinations of KRN5500 and other anticancer drugs on the growth of a human non-small-cell lung cancer cell line, PC14, using a revised three-dimensional model [4].
  • In BLM-rats, extensive pulmonary hemorrhage with diapedesis was observed with KRN5500 i.v. bolus injection at the dose of 3 mg/kg, which is equivalent to 21.0 mg/m2 (level 5) of the Japanese phase I trial [5].

High impact information on KRN5500


Chemical compound and disease context of KRN5500


Biological context of KRN5500


Anatomical context of KRN5500


Gene context of KRN5500

  • Further support for this conclusion is provided by studies which demonstrate that KRN5500 alters the distribution of newly synthesized carcinoembryonic antigen within the secretory pathway, including arrest of this N-glycosylated protein in the Golgi of LS-174T colon carcinoma cells [6].
  • Consequently, these results demonstrated that KRN5500 interacted with, but was hardly transported via, P-gp [12].
  • These observations suggested that KRN5500 may be useful even for the treatment of tumors exhibiting P-gp-mediated MDR [12].
  • In this study, we first investigated the differentiation efficacy of spicamycin and KRN5500 in HL-60 and acute promyelocytic leukemia cell line, NB4, and found that low concentrations of both compounds induced differentiation to a small extent in both cell lines, but markedly induced apoptosis in NB4 cells [9].

Analytical, diagnostic and therapeutic context of KRN5500


  1. KRN5500: a novel therapeutic agent with in vitro activity against human B-cell chronic lymphocytic leukemia cells mediates cytotoxicity via the intrinsic pathway of apoptosis. Byrd, J.C., Lucas, D.M., Mone, A.P., Kitner, J.B., Drabick, J.J., Grever, M.R. Blood (2003) [Pubmed]
  2. Phase I clinical trial and pharmacokinetic study of the spicamycin analog KRN5500 administered as a 1-hour intravenous infusion for five consecutive days to patients with refractory solid tumors. Supko, J.G., Eder, J.P., Ryan, D.P., Seiden, M.V., Lynch, T.J., Amrein, P.C., Kufe, D.W., Clark, J.W. Clin. Cancer Res. (2003) [Pubmed]
  3. Inhibitory effect of a spicamycin derivative, KRN5500, on the growth of hepatic metastasis of human colon cancer-producing tissue polypeptide antigen. Kamishohara, M., Kawai, H., Sakai, T., Uchida, T., Tsuruo, T., Otake, N. Cancer Chemother. Pharmacol. (1996) [Pubmed]
  4. In vitro interactions of a new derivative of spicamycin, KRN5500, and other anticancer drugs using a three-dimensional model. Kanzawa, F., Nishio, K., Fukuoka, K., Sunami, T., Saijo, N. Cancer Chemother. Pharmacol. (1999) [Pubmed]
  5. Incorporation of the anticancer agent KRN5500 into polymeric micelles diminishes the pulmonary toxicity. Mizumura, Y., Matsumura, Y., Yokoyama, M., Okano, T., Kawaguchi, T., Moriyasu, F., Kakizoe, T. Jpn. J. Cancer Res. (2002) [Pubmed]
  6. Selective accumulation of the endoplasmic reticulum-Golgi intermediate compartment induced by the antitumor drug KRN5500. Kamishohara, M., Kenney, S., Domergue, R., Vistica, D.T., Sausville, E.A. Exp. Cell Res. (2000) [Pubmed]
  7. A single intravenous injection of KRN5500 (antibiotic spicamycin) produces long-term decreases in multiple sensory hypersensitivities in neuropathic pain. Kobierski, L.A., Abdi, S., DiLorenzo, L., Feroz, N., Borsook, D. Anesth. Analg. (2003) [Pubmed]
  8. KRN5500, a novel antitumor agent, induces apoptosis or cell differentiation in HL-60 cells. Kawasaki, K., Murakami, T., Ita, M., Sasaki, K., Furukawa, S. Cytometry. (2000) [Pubmed]
  9. Spicamycin and KRN5500 induce apoptosis in myeloid and lymphoid cell lines with down-regulation of bcl-2 expression and modulation of promyelocytic leukemia protein. Zhang, W.J., Ohnishi, K., Yoshida, H., Pan, L., Maksumova, L., Muratkhodjaev, F., Luo, J.M., Shigeno, K., Fujisawa, S., Naito, K., Nakamura, S., Shinjo, K., Takeshita, A., Ohno, R. Jpn. J. Cancer Res. (2000) [Pubmed]
  10. Reduction of the side effects of an antitumor agent, KRN5500, by incorporation of the drug into polymeric micelles. Matsumura, Y., Yokoyama, M., Kataoka, K., Okano, T., Sakurai, Y., Kawaguchi, T., Kakizoe, T. Jpn. J. Cancer Res. (1999) [Pubmed]
  11. Antitumor activity of a spicamycin derivative, KRN5500, and its active metabolite in tumor cells. Kamishohara, M., Kawai, H., Sakai, T., Isoe, T., Hasegawa, K., Mochizuki, J., Uchida, T., Kataoka, S., Yamaki, H., Tsuruo, T. Oncol. Res. (1994) [Pubmed]
  12. The novel anticancer drug KRN5500 interacts with, but is hardly transported by, human P-glycoprotein. Takara, K., Tanigawara, Y., Komada, F., Nishiguchi, K., Sakaeda, T., Okumura, K. Jpn. J. Cancer Res. (2000) [Pubmed]
  13. Population pharmacokinetic modeling and model validation of a spicamycin derivative, KRN5500, in phase 1 study. Takama, H., Tanaka, H., Sudo, T., Tamura, T., Tanigawara, Y. Cancer Chemother. Pharmacol. (2001) [Pubmed]
  14. The effects of KRN5500, a spicamycin derivative, on neuropathic and nociceptive pain models in rats. Abdi, S., Vilassova, N., Decosterd, I., Feroz, N., Borsook, D. Anesth. Analg. (2000) [Pubmed]
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