New drug candidates

In particular, in silico methods are expected to speed up the drug discovery process, to provide a quicker and cheaper alternative to in vitro tests, and to reduce the number of compounds with unfavorable pharmacological properties at an early stage of drug development. Bad ADMET profiles are a reason for attrition of new drug candidates during the development process [9, 10]. The major reasons for attrition of new drugs are ... 

In a typical research and development setting, in the event that a new drug candidate is recognized by the drug-discovery group, then the dissolution rate constant K for that compound under specified hydro-dynamic conditions can be determined from powder dissolution data and practical size analysis by microscopy. 

Pharmaprojects. This service [100] monitors drugs currently under development, tracking all new drug candidates under active international R D— approximately 6000 at any one time. The remaining... 

Morgan, M. E. Liu, K. Anderson, B. D., Microscale titrimetric and spectrophotometric methods for determination of ionization constants and partition coefficients of new drug candidates, J. Pharm. Sci. 87, 238-245 (1998). 

A large number of patent applications has been filed, most recently describing imidazothiazoles [70], oxazolopyridines [71], benzimidazoles [72], benzothiazoles [73] and imidazopyridines [74] as sirtuin modulators, however it is not yet possible to determine which compound classes will prove most promising. Overall, due to their potential applications as new drug candidates for various indications, the class III HDAC inhibitors are currently a rapidly growing field of interest. 

The motivation for conducting toxicological tests for pharmaceutical, chemical intermediates and impurities arises from the need to ensure the health of employees by preventing adverse reactions from occupational exposure. Employers thus secondarily minimize the associated potential for work interruption. Programs in place at many larger companies routinely test new drug candidates and/or isolated synthetic intermediates for the purpose of occupational health hazard evaluation. 

BioPrint is particularly useful in placing the new drug candidates in the context of drugs and related compounds that together make up the history of medicinal chemistry. New candidates are run on the same assays as the BioPrint compounds and the resulting profile is analyzed. Profiles can be analyzed in two different ways each individual hit can be analyzed and assessed for potential ADR liabilities or the entire profile can be used to identify compounds with similar profiles. Potential ADR liabilities are assessed based on those of the similar compounds identified. These two different approaches will be discussed in the following sections. 

Rautio, J., Humphreys, J.E., Webster, L. O., Balakrishnan, A., Keogh, J.P., Kunta, J.R., Serabjit-Singh, C.J. and Polli, J.W. (2006) In vitro P-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates a recommendation for probe substrates. Drug Metabolism and Disposition, 34, 786-792. 

One major difficulty has been that no convincing laboratory model of the drug s clinical effect has yet been established. This has not only hampered mechanistic investigations but has also prevented the rational search, by medicinal chemists, for more specifically effective anti-hypertensive 3-blocking agents. New drug candidates appear to have been selected on the basis of the laboratory pharmacological profile of the molecule and how this profile relates to one or other of the various mode-of-... 

Chapter 4 - Propolis has been used for as a traditional medicine in Eastern Europe as an antifungal, antimicrobial, antiviral, anti-inflammatory, and anticarcinogenic agent. The author isolated three cinamic acid derivatives and one flavanol derivative from Brazilian propolis and determined their structures by spectroscopic analysis. Results were assayed, the anticancer drug potential of these compounds to identify new drug candidates, by determining the... 

As the drug discovery process increased in intensity in the mid- to late 20th century, primarily as a result of the major screening and chemical synthetic efforts in the pharmaceutical industry in industrialized countries worldwide, but also as a result of the biotechnology revolution, the need for increased sophistication and efficacy in (1) how to discover new drugs, (2) how to reproducibly prepare bulk chemicals, (3) how to determine the activity and safety of new drug candidates in preclinical animal models prior to their... 

Studies in the last few years in the fields of genomics and proteomics have made available to us an unprecedented number of targets with which to search for new drug candidates. While knowledge of a particular gene sequence, for example, may not directly point to a specific disease when the sequences are first determined, investigations of their presence in normal and diseased tissues could well lead to a quantitative in vitro test system that is not available today. The same can be said for the field of proteomics, but final decisions on the value of these new technologies cannot be made for some years to come. 

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