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Pre-Clinical Services

Pharmacology and Toxicology Testing: IC50 for Tumor Cell Lines

Half maximal inhibitory concentration, or IC50, is a measurement representing the halfway point in which a compound of interest produces complete inhibition of a biological or biochemical function. This information is derived based on pharmacological data in reference to a dose-response curve. As the dosage of an inhibitory compound is increased, the biological function it affects decreases, and the point at which the concentration of the inhibitor has suppressed 50% of the biological activity is referred to as the IC50. IC50 is most often used as a measurement of antagonist, or inhibitory drug potency, as well as a quantification of the toxicological effects of inhibitory compounds.

During the development of Investigational New Drug (IND) applications, in vitro and in vivo toxicology testing studies are important to determine the threshold of inhibition of biological functions and effects of the compound on metabolism. In an effort to evaluate new pharmaceutical drugs and therapeutic treatments, cancer cell lines are used as in vitro models to screen the candidate drugs. We maintains a large library of cell lines that can be used for in vitro IC50 studies (see Table below for some selected examples) and has the capacity to utilize client-provided cell lines as well.

Table. Selected cancer cell lines available for in vitro IC50 testing:

Disease / Tumor Type: Cell Line / ID
Breast Adenocarcinoma SKBR3, MDA-MB, MCF7
Burkitt’s Lymphoma Daudi, Raji, Ramos
Colon Carcinoma Caco2, LS174T, SW480
Lung Adenocarcinoma NCI-H460, NCI-H23
Leukemia K-562, CCRF-CEM )
Lewis Lung Carcinoma Calu-3, Calu-6, A549
Kidney MDCK, Cos7, HEK293
Melanoma J774A.1, SK-MEL-28
Neuroblastoma SK-N-SH, Neuro-2a
Osteosarcoma MG-63, SK-OV-3
Ovarian Adenocarcinoma Beta-TC-6, CHO-K1
Pancreatic Carcinoma Capan-1, MIA PaCa-2
Prostate Carcinoma LNCaP, DU145
Rhabdomyosarcoma Detroit 551

In Vivo Toxicology Service (Mouse, Rat)

Preclinical in vivo toxicology is the study of toxic effects of chemical substances based on statistical and quantitative analysis.  Toxicology studies can include acute, subchronic and chronic toxicity tests.

Acute toxicology studies focus on the toxicological effects following a single large dose of the substance of interest. For longer term studies subchronic and chronic studies are done to simulate long term use of the drugs and their subsequent adverse effects. Subchronic toxicology studies include repeated small dosages of the test substance over a period of time up to 90 days. While chronic toxicology studies focus on the long term effects of the test substance over periods of months to years. Implications of these toxicology studies can lead to phase 1 clinical trial should the test substance show promising results and minimal toxicological, carcinogenic and mutagenic effects.

Studies can range from acute to chronic exposure treatments. The variation in time and amount of test substance in taken by the subject helps create dose response curves to determine thresholds of biological activity associated with the test substance as well as levels of toxicity. Through in vivo toxicology IND studies, a variety of factors are tested to determine everything from acute toxicity to reproductive toxicity.

Another focal point of in vivo toxicology focuses on the route of administration of investigative new drugs (IND). The ability of a drug to reach its target in a living system can unintentionally be deterred by immune system mechanisms, metabolic processes, and similarly natural mechanisms. This is the problem faced following in vitro studies in which INDs are no longer directly targeting the desired cells but are faced with a living biological system in which their target is one of many. As a result, various drug administration routes are explored to determine toxicity and benefits when such routes are taken. Evaluation of drug administration routes should anticipate clinical results and optimize beneficial efficacy. The study should determine a safe and effective procedure for administration, as well as dosage for the drug to prevent any adverse affects.

Identification of potential toxicological side effects is very important to the advance of INDs to phase 1 clinical trial. Such side effects can have an impact on the future health of the subject, its progeny, and overall survival rate. Potential side effects can be detrimental to the immune system, the integrity of the DNA and the functionality of vital organs. As a result additional tests can be run to study sensitivity, irritation, mutagenic and/or carcinogenic properties, reproductive toxicity and immunotoxicity. Additional studies focusing on pharmacodynamics, pharmacokinetics and ADME processes also contribute greatly to the INDs application.

Included in a full report summary of toxicity are urinalysis, bioanalysis, chemistry, pharmacokinetics, pharmacodynamics, and histopathology results.

To find out more details about this custom service, Please request a quote today.