The term "undruggable" is often use in drug discovery. As far as I understand it, it means "for which no inhibitor has been found so far".
It's a fuzzy, non-satisfying, definition.
What is an undruggable target?
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I doubt a proper definition of the word "undruggable" would be found anywhere. The word is used throughout medchem books without any explanations, but the word "druggable" is more widely used.
As a note, I also found the word "druggable" used in conjuction with cellular pathways, genome, cell types, or binding sites, not only with molecular targets e.g. proteins.
As such, an "undruggable" target (or pathway, or cell type) is simply considered "unsuitable for pharmacological modulation". Check the following references, in regard to protein targets.
From Drug Discovery and Development – Present and Future, Edited by Izet M. Kapetanovic (2011):
In this context, one of the most challenging tasks is the identification of the right target and more importantly whether this target is ‘druggable’. For example, although we know that RAS mutations are an early component of tumorigenesis and are identified in approximately 30% of human cancers, attempts to target RAS have been unsuccessful to date as complex molecular structures constrain binding to the active site or pocket
The successful development of such agents is of course complex but can be simplistically considered as having three key components: the right target (strong biologic rationale, druggable), the right drug selective, right formulation, tolerable side-effect profile) and the right biomarker (reproducible, validated)
Many stones are still left unturned, perhaps due to the lack of interest or belief that so-called “undruggable” proteins can be successfully targeted.
From Burger's 6th ed. (2003):
A number of these molecular targets are considered "druggable" or suitable for pharmacological modulation, including the 5-HT-R..."
From Flow Cytometry in Drug Discovery and Development (2011, John Wiley & Sons):
a target may be identified from patient samples, but this target may be known to be undruggable based on prior screening efforts.