[Protein synthesis inhibitor--antitumor activity and mode of action of KRN 5500].

Abstract

KRN 5500 is a new semi-synthetic antitumor compound derived from spicamycin and has a unique structure. The compound showed a broad spectrum of antitumor activity against human colon, stomach, esophageal, breast and lung cancer xenografts in nude mice. Therapeutic efficacy of KRN 5500 against liver metastasis of COL-1 human colon cancer scid mice was examined. The treatment with KRN 5500 inhibited tumor growth in the liver and reduced the serum TPA concentration to a normal level. KRN 5500 inhibits protein synthesis in rabbit reticulocyte lysates. Among several metabolites of KRN 5500, only SAN-Gly showed a potent inhibitory activity against protein synthesis in reticulocyte lysates. TLC analysis of KRN 5500 metabolites using 7 human colon cancer cell lines and 3 normal cell lines demonstrated a correlation between the cytotoxicity of KRN 5500 and converting activity from KRN 5500 to SAN-Gly. These results indicate that SAN-Gly is the intracellular active metabolite and that converting activity from KRN 5500 to SAN-Gly is the major determinant of KRN 5500 cytotoxicity.

• Authors: H Kawai
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 24 Issue 11 Pg. 1571-7 (Sep 1997) ISSN: 0385-0684 [Print] Japan
• PMID: 9309156 (Publication Type: Journal Article, Review)

Chemical References

• Antibiotics, Antineoplastic
• Protein Synthesis Inhibitors
• Purine Nucleosides
• KRN 5500

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Breast Neoplasms (pathology)
• Cell Division (drug effects)
• Colonic Neoplasms (pathology)
• Humans
• Lung Neoplasms (pathology)
• Mice
• Neoplasm Transplantation
• Protein Synthesis Inhibitors (pharmacology)
• Purine Nucleosides (chemistry, pharmacology)
• Rabbits
• Stomach Neoplasms (pathology)
• Tumor Cells, Cultured (drug effects)