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Immunotoxicity is defined as the toxicological effects of xenobiotics including pharmaceuticals on the functioning of the immune system and can be induced in either direct or indirect ways. Direct immunotoxicity is caused by the effects of chemicals on the immune system, leading to immu ...

The identification of small drug-like compounds that selectively inhibit the function of biological targets has historically been a major focus in the pharmaceutical industry, and in recent years, has generated much interest in academia as well. Drug-like compounds are valuable as ch ...

Understanding the three-dimensional aspects of drug-receptor interactions and their specificity at the molecular level has become a focal point in modern drug discovery. Herein, we describe a set of methods by which the binding site on a protein can be located and mapped and the protein–liga ...

Computer-aided approaches have been widely used in pharmaceutical research to improve the efficiency of the drug discovery and development pipeline. To identify and design small molecules as clinically effective therapeutics, various computational methods have been evalu ...

Prostate cancer is considered the most common cancer form among males in Western countries. Very limited options are available for the treatment of advanced metastatic prostate cancer. More than 50% of today’s anticancer drugs are natural products or derived from a natural origin. To disco ...

Real-time RT-PCR using a TaqMan� fluorogenic detection system is a simple and sensitive assay for quantitative analysis of gene transcription. This method is of potential usefulness in quantifying mRNA of a target gene in autopsy material that has undergone only a small amount of postmortem ...

There is increasing recognition that pharmacogenetic polymorphisms affecting drug metabolism are valid biomarkers affecting drug safety and efficacy. This is shown by the inclusion of information about genetic polymorphisms affecting drug metabolism on drug labels with, in s ...

Following oral administration to animals and humans, drugs are absorbed, transported via portal circulation to the liver, and metabolized primarily via this organ. In general, drugs are predominantly metabolized by the oxidation of parent drug, which is typically mediated by cytochr ...

The processes of modern drug discovery and development rely on the ability to obtain information regarding new chemical entities as quickly and inexpensively as possible. For this reason, laboratories have developed various in vitro techniques that can help to minimize undue investm ...

Glucuronidation catalyzed by the UDP-glucuronosyltransferases (UGTs) is a major pathway for drug metabolism and elimination in humans. Identification of the UGTs responsible for glucuronidation of existing and novel drugs will assist in the prediction of adverse reactions re ...

This chapter provides a detailed description of methodology used to assess the cytochrome P450 inhibition potential of small molecules using fluorometric substrates in a multiwell plate format. Inhibition of cytochromes P450 can result in drug-drug interactions or, in some cases, t ...

Evaluation of lead compounds for P450 inhibition in human liver microsomes has been widely accepted as an in vitro approach to assess drug interaction potential. This chapter describes a detailed traditional CYP inhibition protocol for six major isoforms: 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. Mic ...

Metabolic drug-drug interactions occur when a drug A alters the pharmacokinetics of a coadministered drug B by either inhibiting, activating, or inducing the activity of the enzyme(s) that metabolize drug B. Inhibitory drug-drug interactions could result in serious adverse effects, i ...

32P-Postlabeling analysis is a powerful technique for the detection, quantification, and identification of DNA adducts induced by mutagens or carcinogens, including large numbers of drugs and their metabolites. The method includes enzymatic digestion of a deoxyribonucleic a ...

In this chapter, the experimental details are described for the utilization of cytochrome P450-mediated reactions to examine the potential of chemicals (drugs) to be activated to reactive species, leading to the formation of covalent deoxyribonucleic acid (DNA) adducts. Methods for ...

The comet assay, also called the single-cell gel electrophoresis (SCGE) assay, is a simple, rapid, and sensitive technique for detecting deoxyribonucleic acid (DNA) damage at the level of individual eukaryotic cells. The types of DNA damage that can be observed with this method are DNA double- ...

In the drug discovery process, the lead candidates must have proper physicochemical properties, in addition to affinity and potency, in order to have a better chance of success in development. Many pharmacologically active compounds fail to become drugs because of poor bioavailabilit ...

32P-Postlabeling analysis is an ultrasensitive method for the detection of DNA adducts, such as those formed directly by the covalent binding of carcinogens and mutagens to bases in DNA, as well as other DNA lesions resulting from modification of bases by endogenous or exogenous agents (e.g., o ...

The original 32P-postlabeling method developed by Randerath and his colleagues has been modified to detect a single type of adduct as a single spot in thin-layer chromatography (TLC), because some types of adducts gave multiple adduct spots by the original method. In the remodified methods, D ...

A protocol is described for the isolation of DNA and subsequent preparation of samples for the measurement of adduct levels by accelerator mass spectrometry (AMS). AMS is a highly sensitive technique used for the quantification of adducts following exposure to carbon-14- or tritium-lab ...