MedKoo product information:

KRN5500

KRN5500 is a semisynthetic derivative of the nucleoside-like antineoplastic antibiotic spicamycin, originally isolated from the bacterium Streptomyces alanosinicus. KRN 5500 inhibits protein synthesis by interfering with endoplasmic reticulum and Golgi apparatus functions. This agent also induces cell differentiation and caspase-dependent apoptosis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

KRN5500 is available as a solution for intravenous (IV) administration.  KRN5500 was discovered in an effort to identify new agents that induced differentiation of myeloid leukemia cells. Safety and efficacy data from Phase I trials have been leveraged to support DARA Therapeutics’ active IND and ongoing Phase 2a clinical trial.  The objective of this Phase 2a feasibility study is to determine the potential of KRN5500 (a spicamycin analogue) to be a breakthrough medicine for the treatment of neuropathic pain in cancer patients. Four clinical trials have been conducted in cancer patients, including one in Japan and 3 in the United States.  Three of these studies are complete; the fourth was closed to patient accrual and treatment in December 2004.  A total of 91 patients with solid tumors have been treated with single IV KRN5500 doses of up to 21 mg/m2 and weekly doses of up to 42 mg/m2.  While KRN5500 has not shown anti-cancer efficacy in any trial, its use in pain elimination is encouraging. (source: http://www.darabiosciences.com/krn5500.htm).

Current developer:    Dara BioSciences, Inc

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6: Supko JG, Eder JP Jr, Ryan DP, Seiden MV, Lynch TJ, Amrein PC, Kufe DW, Clark JW. 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. Clin Cancer Res. 2003 Nov 1;9(14):5178-86. PubMed PMID: 14613997.

7: Yamamoto N, Tamura T, Kamiya Y, Ono H, Kondoh H, Shirao K, Matsumura Y, Tanigawara Y, Shimada Y. Phase I and pharmacokinetic study of KRN5500, a spicamycin derivative, for patients with advanced solid tumors. Jpn J Clin Oncol. 2003 Jun;33(6):302-8. PubMed PMID: 12913085.

8: Kobierski LA, Abdi S, DiLorenzo L, Feroz N, Borsook D. A single intravenous injection of KRN5500 (antibiotic spicamycin) produces long-term decreases in multiple sensory hypersensitivities in neuropathic pain. Anesth Analg. 2003 Jul;97(1):174-82, table of contents. PubMed PMID: 12818962.

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11: Mizumura Y, Matsumura Y, Yokoyama M, Okano T, Kawaguchi T, Moriyasu F, Kakizoe T. Incorporation of the anticancer agent KRN5500 into polymeric micelles diminishes the pulmonary toxicity. Jpn J Cancer Res. 2002 Nov;93(11):1237-43. PubMed PMID: 12460465.

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13: Abdi S, Vilassova N, Decosterd I, Feroz N, Borsook D. The effects of KRN5500, a spicamycin derivative, on neuropathic and nociceptive pain models in rats. Anesth Analg. 2000 Oct;91(4):955-9. PubMed PMID: 11004056.

14: Stine KC, Warren BA, Saylors RL, Becton DL. KRN5500 induces apoptosis (PCD) of myeloid leukemia cell lines and patient blasts. Leuk Res. 2000 Sep;24(9):741-9. Erratum in: Leuk Res 2000 Dec;24(12):1063. PubMed PMID: 10978778.

15: Zhang WJ, Ohnishi K, Yoshida H, Pan L, Maksumova L, Muratkhodjaev F, Luo JM, Shigeno K, Fujisawa S, Naito K, Nakamura S, Shinjo K, Takeshita A, Ohno R. Spicamycin and KRN5500 induce apoptosis in myeloid and lymphoid cell lines with down-regulation of bcl-2 expression and modulation of promyelocytic leukemia protein. Jpn J Cancer Res. 2000 Jun;91(6):604-11. PubMed PMID: 10874212.

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23: Kawai H. [Protein synthesis inhibitor--antitumor activity and mode of action of KRN 5500]. Gan To Kagaku Ryoho. 1997 Sep;24(11):1571-7. Review. Japanese. PubMed PMID: 9309156.

24: Yoshioka E, Morino M, Tanaka H, Shinkai H. Manual and automatic extraction and high-performance liquid chromatographic determination of a spicamycin derivative, KRN5500, in rat plasma. J Chromatogr B Biomed Sci Appl. 1997 Apr 11;691(2):371-5. PubMed PMID: 9174273.

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26: Kamishohara M, Kawai H, Sakai T, Uchida T, Tsuruo T, Otake N. Inhibitory effect of a spicamycin derivative, KRN5500, on the growth of hepatic metastasis of human colon cancer-producing tissue polypeptide antigen. Cancer Chemother Pharmacol. 1996;38(6):495-8. PubMed PMID: 8823489.

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28: Kamishohara M, Kawai H, Sakai T, Isoe T, Hasegawa K, Mochizuki J, Uchida T, Kataoka S, Yamaki H, Tsuruo T, et al. Antitumor activity of a spicamycin derivative, KRN5500, and its active metabolite in tumor cells. Oncol Res. 1994;6(8):383-90. PubMed PMID: 7894087.