Wombat

ZINC is provided by the Shoichet Lab, in the Department of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF). 2.3.2.3 Free Tools to Filter Compound Libraries FAF-Drugs2 262 is a free adaptable tool for the ADME Tox filtering of electronic compound collections. FAF-Drugs2 is a command-line utility program (e.g., written in Python) based on the open source chemistry toolkit OpenBabel. FAF-Drugs2 performs various physicochemical calculations,...

Physicochemistry Pharmacokinetics Drug Like and Lead Like Concepts

Drug molecules generally act on specific targets, and upon binding to the receptors, hopefully exert a desirable alteration of the target cellular activities. Before interacting with the receptor, drug molecules must travel from the entry point through the body to reach the site of action at the desired concentration and with sufficient duration. After executing their activities, drug molecules should be eliminated from the organism. For most drugs, the preferred route of administration is by...

Voyage Through The Digestive System

It takes 12-48 h for ingested food to complete its voyage through the digestive system. The food first arrives in the mouth (pH 7) where it is chewed and exposed to its first set of enzymes, called salivary enzymes. Subsequently, the food travels down the esophagus to the stomach (pH 1-2), which undergoes receptive relaxation as it fills to a capacity of 2 L or more (Figure 1.1). The next stage in the digestive system is the small intestine where chemical digestion continues and most nutrients...

Toxicity Definitions [54

Acute toxicity is the toxic effects from a substance resulting from a single exposure or several exposures during less than 24 h from a single dose, occurring within 14 days after administration. Carcinogenicity is toxicity due to agents that promote cancer and or increase its propagation. Clastogenicity refer to a form of mutagenicity due to chromosome breakage. Chronic toxicity is the toxic effects from repeated exposures to a substance over a long-term dosing (months or years). Cytotoxicity...

Preparing a Compound Collection Materials and Methods

One concept regarding ADME Tox in silico filters is that the physicochemical properties of a compound are expected to determine its pharmacokinetic and metabolic behavior in the body. In general, molecules with inadequate initial properties (ADME Tox profile) usually increase the development costs and tend to put significant burden to patients even if they do not fail in clinical trials. Further, a compound collection may be prepared for a chemical biology project or for drug discovery, and in...

Plasma Protein Binding

The binding of drugs to plasma proteins and to human serum albumin (HSA) in particular has ADME Tox implications affecting clearance, volume of distribution, and efficacy. Drugs can bind to a variety of particles in the blood, including red blood cells, leukocytes, and platelets, as well as proteins HSA (particularly acidic drugs), a1-acid glycoprotein (AAG) (basic drugs), lipoproteins (neutral and basic drugs), erythrocytes, and a,p,y-globulins. From a recent analysis of 2939 diverse drugs...