Are transcription factors Druggable?

Recent developments in the fields of cancer biology and genetics have significantly increased our understanding on how to validate new drug targets, including transcription factors, which have been considered “undruggable.” Unlike enzymes, ion channels, and cell membrane receptors, transcription factors do not possess …

Are transcription factors good drug targets?

A principal reason why TFs are considered highly alluring therapeutic targets is that transcriptional dysregulation plays an essential role across a wide variety of diseases3 (Table 1).

What are transcriptional targets?

Identification of the targets of each transcription factor provides information about individual processes and how transcription factors interact in a transcriptional network. These networks can then be used to describe a particular cellular process, or even something as complicated as embryonic development [1,2].

What is a druggable target?

Druggability is a term used in drug discovery to describe a biological target (such as a protein) that is known to or is predicted to bind with high affinity to a drug. Disease relevance alone however is insufficient for a protein to become a drug target. In addition, the target must be druggable.

Why is it difficult to target transcription factors?

As such, transcription factors could be considered prime targets for drug development. However, transcription factors have been historically difficult to target, owing in part to the fact that they typically exert their activity via protein-protein and/or protein-DNA interactions.

Why are transcription factors of interest in pharmaceutical development?

Like cell-surface receptors, gene-specific transcription factors are attractive drug targets because they have substantial structural diversity. When considering systemic administration of drugs, gene-specific transcription factors have the added advantage of substantial specificity in their mode of action.

What is transcriptional addiction?

Cancer arises from genetic alterations that invariably lead to dysregulated transcriptional programs. These dysregulated programs can cause cancer cells to become highly dependent on certain regulators of gene expression.

What is an example of a transcription factor?

The Hox transcription factor family, for example, is important for proper body pattern formation in organisms as diverse as fruit flies to humans. Another example is the transcription factor encoded by the sex-determining region Y (SRY) gene, which plays a major role in determining sex in humans.

How do you identify the transcription factor?

DNA BINDING ASSAYS USED TO STUDY TRANSCRIPTION FACTORS. The principal strategy in identifying and characterizing transcription factors is based on their ability to recognize and interact with specific DNA sequences present in the promoters of eukaryotic genes.

What makes a target not druggable?

A target’s druggability is usually estimated by classifying it with known gene families that have previously been successfully targeted with drugs. But as the targets of some marketed drugs are considered as conventionally non-druggable, this approach comes with limitations.