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Calicheamicin

Topic editor
Steven G. Gilbert
Lead author
Sean Foley


Chemical Structure


Just the facts


Physical Information
Name: Calicheamicin, Mylotarg®, Gemtuzumab Ozogamicin
Use: Treatment for acute myelogenous leukemia
Source: Natural product of bacteria found in caliche clay
Recommended daily intake: Varies from patient to patient
Absorption: Administered intravenously (long elimination half-life)
Sensitive individuals: fetus, children, some adults
Toxicity/symptoms:
Regulatory facts: Safety and efficacy trials conducted
General facts: Approved by the FDA May 17, 2000
Environmental: Calicheamicin is a natural metabolic product of bacteria
Related chemotherapy agents: Mylotarg is a "first in class" antibody-targeted chemotherapy agent
Recommendations: Mylotarg® must be prescribed and administered by an experienced physician


History


Calicheamicin was discovered in 1981 (or 1987) by a scientist from Lederle Labs (now Wyeth) while on vacation in Kerrville, Texas (Other sources site Waco, Texas). The scientist collected a soil sample, which consisted of caliche clay, and sent it back to the lab for testing. Scientists grew a culture of the soil sample and found tiny bacteria within the sample produced a compound called "calicheamicin". Calicheamicin was found to be an incredibly potent cytotoxic agent and worked by destroying the DNA of cancer cells. Calicheamicin was so potent that it also destroyed the DNA of normal cells (1,000 to 10,000 times more [cytotoxic] to normal cells than drugs already on the market)..

Dr. George Ellestad, Dr. Janis Upeslacis and Dr. Philip Hamann (Wyeth) began studying calicheamicin in order to better understand its mechanism. Together, they devised a plan to link calicheamicin to an antibody that specifically targeted cancer cells. In this way, they were able to keep calicheamicin from destroying normal cells because the antibody linker served as a "by pass" taking calicheamicin directly to the Cancer cell.

The FDA approved this new antibody-linked calicheamicin (Mylotarg) on May 17, 2000, almost 20 years after its discovery. Mylotarg is the very first drug in its class (antibody-targeted [chemotherapy] agents) and is used in the treatment of acute myelogenous [leukemia]. Remission rates of greater than 30% have been reported (Clinical Trials).

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