Drug development program

Lead structure According to Valler and Green s definition a lead structure is a representative of a compound series with sufficient potential (as measured by potency, selectivity, pharmacokinetics, physicochemical properties, absence of toxicity and novelty) to progress to a full drug development program [12]. 

T. R. Sweeney, M Survey of Compoundsfrom the Hntiradiation Drug Development Program of the U.S. Army Medical Research and Development Command Walter Reed Army Institute of Research, Washington, D.C., 1979. 

In this chapter we describe the current insights into the evolution of viruses under pressure of antiviral therapy and the potential impact on viral fimess. As most recent work in this field has been done in the field of human immunodeficiency virus (HIV), we use the evolution of this virus as the basis for the chapter. Subsequently, we describe resistance evolution for Hepatitis B virus (HBV), where large progress has been made in recent years. Furthermore, we describe the resistance development for Hepatitis C virus (HCV), for which a very active drug development program is undertaken by several pharmaceutical companies. Finally, we discuss resistance evolution for Influenza. 

As members of the GPCR superfamily have historically dominated drug development programs, so too has interest in chemokine receptors as therapeutic targets. 

We have developed the efficient synthesis of the SERM drug candidate 1 and successfully demonstrated the process on a multiple kilogram scale to support the drug development program. A novel sulfoxide-directed borane reduction of vinyl sulfoxides was discovered. The mechanistic details of this novel reaction were explored and a plausible mechanism proposed. The sequence of asymmetric oxidation of vinyl sulfoxides followed by stereospecific borane reduction to make chiral dihydro-1,4-benzoxathiins was applied to the asymmetric synthesis of a number of other dihydro-1,4-benzoxathiins including the sweetening agent 67. 

The analysis of safety data may require larger data sets, so care in ensuring that a consistent phenotype is collected will be important. Furthermore, the benefit to the drug development program could be that additional data to predict adverse events could be available at the time a drug is marketed. 

Drug safety is one of the first places where we are likely to see the benefits of pharmacogenetics. Pharmacogenetic approaches differ according to the rate of adverse events. Common adverse events with rates of 1% or more can be evaluated during a traditional drug development program. Com-... 

Pfizer employs more than 100,000 people, of which 12,000 are medical researchers. The company focuses its new drug development program in 11 therapeutic areas ... 

Broadly, the drug development program covers the following. 

Early on in the drug development program, only small amoimts of material are available for crystallization studies. Parallel crystallization technique in test tubes allows for the identification of many solvent systems using small amoimts of material. On a small scale, it is not easy to control the rate of cooling or the rate of evaporation to achieve supersaturation. However, the antisolvent addition strategy to achieve supersaturation in combination with seeding, allows rapid identification of several crystallization systems using a minimum amount of compound. 

Current efforts favor tumor cell line tests, conducted by the National Cancer Institute (NCI) drug development program [62]. In the current NCI anticancer screen, each compound is tested against 60 human tumor cell lines derived from several cancer types (lung, colon, melanoma, kidney, breast, ovary, brain, leukemia). The tumor cells are seeded on 96-well microtiter plates and pre-incubated for 24 h. The test agents are then added to the wells (five 10-fold dilutions 0.01 -100 pmol/1) and are incubated for 48 h with the tumor cell lines. At the termination of the assay, the cells are fixed in situ with trichloroacetic acid (TCA), washed and dried. Sulforhodamine B (SRB), a dye that binds to the basic amino... 

Major customers for CRO services are the large global pharma (ceutical) companies. Half a dozen big pharma s (Pfizer, Glaxo SmithKline, Sanofi-Aventis, AstraZeneca, Johnson Johnson, and Merck) alone absorb an estimated 30% of all CRO spending. As for CMOs and also for CROs, biotech startup companies with their dichotomy between ambitious drug development programs and limited resources are the second most promising prospects after big pharma (see Section 12.3). 

Graffner, C., M. E. Johansson, M. Nicklasson, and H. Nyqvist. 1985. Preformulation studies in a drug development program for tablet formulatiodsPharm. Sci74 16-20. 

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