Candidate status

Once a hit is elevated to the status of a lead compound, the activity of the lead must be increased. This is accomplished by making structural modifications to the lead compound. The link between modification of a lead s structure and changes in activity is called a structure-activity relationship (SAR). As it becomes better understood, the SAR of a lead guides the medicinal chemistry team as it seeks the best methods of increasing the lead s activity. Once the lead has been adequately optimized and shows desirable properties, the lead then graduates to candidate status. Standardized safety testing in animals, called animal trials, is the next step. A more detailed discussion of the lead optimization process may be found in Chapters 11 and 12. 

If a lead molecule emerges from these additional studies on SAR, absorption, distribution, metabolism, and excretion (ADME) and toxicity, it acquires the clinical drug candidate status. After a short toxicological smdy it fulfills the criteria required for administration to humans for initial clinical studies. 

Akron Research Commercialization Corp. has recently disclosed a drug candidate based on Ag-NHC complexes (Silvamist ). These NHC complexes were proven efficient for the treatment of respiratory diseases, and the company is currently applying for Investigational New Drug (IND) status with the FDA (US Food and Drug Administration)... 

The choice of therapy for metastatic disease is based on the site of disease involvement and presence or absence of certain characteristics (i.e., hormonal status of the primary tumor and disease location). For example, patients who experience a long DFS following local-regional therapy or have disease that is located primarily in the bone or soft tissue likely will respond to endocrine therapy. Patients with asymptomatic visceral involvement (e.g., liver or lung) may be candidates for hormonal therapy depending on the clinical circumstance (generally... 

Verify the histology and clinical stage of disease. Evaluate the patient s performance status. Is the patient a surgical candidate How does this influence treatment recommendations ... 

Wilkinson also notes the importance of emotional development in early life poor attachment and emotional trauma in early childhood affects health. As he notes, there are observed associations between health and social status, between health and friendship, and between health and early emotional development. All three of these must be considered prime candidates for sources of social anxiety. 

The exclusion method also includes instances in which drug candidates are themselves excluded from causation status because a nondrug etiology is clearly demonstrable (environmental or occupational factors, radiation injury, the underlying disease of the patient, or a comorbid state) that can reasonably account for the clinicopathology findings. 

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