Unlike single kinase inhibitors (SKIs), NSKIs are designed to target multiple signalling kinases with high specificity in order to hit a number of distinct inflammatory pathways simultaneously.
Likewise, redundancy is often observed between the inputs of multiple signalling pathways, presenting a significant obstacle in using individual signalling pathway inhibitors in the treatment of cancer and inflammatory conditions 94, 95.
Numerous targeted small molecule inhibitors are being developed as a new approach to cancer therapy; however, as tumours often have defects in multiple signalling pathways single agent antitumour activity is modest thus combination treatment is being investigated.
The inhibitor of cdk activity p27KIP1 is an important example of a protein whose expression and activity is modulated by multiple signalling pathways including steroid receptors.
In certain therapeutic areas such as oncology, the efficacy of a drug often depends on its ability to specifically bind to multiple targets and elicit polypharmacological effects (i.e., interference with multiple signaling pathways), with kinase inhibitors being a prime example.
To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC (against PI3K, Akt, JNK, ERK, p38 MAPK and NF-κB-p65, respectively) were used.
Because HSP90 inhibitors impair multiple signal transduction pathways, resulting in decreased cell survival and DNA repair [ 20, 24, 46], our data showed that functional inactivation of Brca1 is particularly vulnerable to this combination.
Considering BAD's facility to function as a switch between life and death, and its regulation via both phosphorylation and localization, the development of inhibitors of multiple signaling proteins, as well as of molecules that interfere with protein protein interactions, would be valuable.
Nintedanib is an oral angiokinase inhibitor targeting multiple signaling pathways implicated in the pathogenesis of MPM, including the VEGF receptor.
MLS-2438 as a Src inhibitor suppresses multiple signaling proteins and represents a promising lead compound for development of new anticancer therapeutics, especially for melanoma.
