Genomics: success or failure to deliver drug targets?

Target mRNA inhibition by oligonucleotide drugs in man

“…They are well suited to the modern paradigm of pharmaceutical research which begins with the gene coding for a disease-relevant target. Where a target represents a new mechanism of action and is being investigated for the first time in patients there is a steep learning curve and a high probability of failure (6). We examined 26 oligonucleotide drug/target combinations which are, or were recently, in phase 2 clinical trials or above according to the Thomson Reuters Integrity database (Table 1).…”

“…Although new mechanisms of action offer the possibility of breakthrough treatments, the success rate of drug development involving unvalidated targets is lower than for validated targets (5). One analysis gave the probability of success (first dose in patients to approval) for a new mode of action as 9%, compared with 23% for a drug with an established mechanism (6). A second report put the value at 7% (small-molecule drugs; phase 1 to launch) (7).…”

In SilicoADME/Tox Predictions

“…Increasing the numbers of available and validated test sets for in silico computations should also help in this endeavor. Pharmacokinetic and the pharmacodynamic profiles are complex functions of properties; however, one might expect that at some points, after years of chemogenomics and systems chemical biology research, the drug discovery community will fully understand relationships between physical properties of compounds and in vitro-in vivo behaviors [9,60,[63][64][65][66][67][68][69][70][71]. Figure 2.6 Overview of key ADME/Tox processes.…”

Peptides as Drugs: Discovery and Development

“…The term " druggable genome " was coined with the intent to delimit the subset of molecular targets for which orally available, commercial drugs could be developed. The majority of currently used drugs are directed towards classical druggable targets such as enzymes, G -protein coupled receptor s ( GPCR s), carriers and nuclear hormone receptor s ( NHR s) and ion channels [12] . The term " druggable " refers to targets which exhibit protein folds capable of interacting with drug -like chemical compounds.…”