VRCTC-310 — A novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity |
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Authors: | Robert A Newman Juan C Vidal Luis J Viskatis Jill Johnson Martin A Etcheverry |
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Institution: | (1) Department of Clinical Investigation, The University of Texas, M.D. Anderson Cancer Center, 77030 Houston, TX, USA;(2) Ventech Research Inc., Cambridge, MA, USA;(3) Drug Synthesis and Chemistry Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD, USA |
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Abstract: | Summary Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute.In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis.In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicityin vitro and which has demonstrated interestingin vivo antitumor efficacy. |
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Keywords: | VRCTC-310 animal venom phospholipase A2 cardiotoxin crotoxin Lewis lung carcinoma |
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