Other kinases with Kd <100 nM

The designation "Other kinases with Kd <100 nM" is a categorical descriptor used in pharmacological profiling rather than a specific biological target. It refers to a subset of the kinome that demonstrates high binding affinity to a particular compound, characterized by a dissociation constant (Kd) of less than 100 nanomolar (Davis et al., 2011, Nature Biotechnology). In drug discovery, identifying these "other" kinases is crucial for evaluating the selectivity of kinase inhibitors and predicting potential off-target effects. Kinases as a class are essential enzymes that regulate nearly every cellular process by transferring phosphate groups to proteins, thereby altering their function (Manning et al., 2002, Science). When a drug candidate interacts with multiple kinases beyond its intended primary target, it can lead to unintended systemic consequences or unexpected therapeutic benefits. This classification helps researchers understand the broader impact of a molecule on the cellular signaling landscape and guides the optimization of chemical leads to improve safety and efficacy. High-affinity binding to off-target kinases is a common cause of toxicity in kinase inhibitor development (Karaman et al., 2008, Nature Biotechnology). Therefore, this grouping is a standard metric in kinome-wide competition binding assays to define the "selectivity hit" profile of a small molecule.

Other names

Off-target kinasesSecondary kinase targetsKinome selectivity hits

Inhibition of kinase catalytic activity via competitive or non-competitive binding at the ATP-binding site or allosteric sites.