Kinase Inhibitor Scaffolds

PDB code Res. Kinase Species Inhibitor class IC50 (nM) Ref. 

PKCa EC50 50 (ilWI PDGFR ECS0 100 nM Abl EC50 30 nM 

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Reynolds RC, Ananthan S, Faaleolea E et al (2012) High throughput screening of a library based on kinase inhibitor scaffolds against Mycobacterium tuberculosis H37Rv. Tuberculosis (Edinb) 92 72-83... 

The pyrrolo 2,l-/][l,2,4Jtriazine nucleus has been identified as a novel kinase inhibitor template which effectively mimics the well known quinazoline kinase inhibitor scaffold <04JMC4054>. 

In contrast to the previous examples, potent CDK inhibitors that are based on a [l,3,6]-trisubstituted-pyrazolo-[3,4-d]-pyrimidine-4-one kinase inhibitor scaffold [56] have recently been found (using Y3H) to exhibit a remarkable proteome-wide specificity for a relatively small number of CDKs/CRKs [52]. These included kinases other than the known targets CDK1/2, some of which have been implicated in cellular processes associated with cellular proliferation or, alternatively, the pathogenesis of diseases other than cancer. Thus, a... 

Other promiscuous pharmacophores cited by Peters are the kinase pharmacophores. This may be particularly difficult to avoid as hits, since many corporate collections are populated with kinase inhibitor scaffolds due to large number of programs and ease of synthesis. However, given the vast... 

In addition to the preceding kinase inhibitors, a number of patents describe compounds that are claimed to be active against PKB (e.g., diamino tri-azines, diaminopyrimidines or 5-aminocarbonylindazoles) [1,144]. Although in general no kinase inhibitory data are provided in these patents, the diverse chemical scaffolds covered in these specifications may represent promising new chemotypes for the future generation of PKB kinase-selective inhibitors. 

Pfizer (Pharmacia) disclosed the development of potent Aurora-A kinase inhibitors containing the 3-aminothieno[3,2-c]pyrazole (80) and 3-amino-furo[3,2-c]pyrazole (81) scaffolds [195,196]. Extensive data was not reported... 

Fig. 3 A collection of potent organoruthenium protein kinase inhibitors based on the metallo-pyridocarbazole scaffold...

Phthalazines were discovered as scaffolds for both PDE5 inhibitors and kinase inhibitors. Similarly, anthranilic acid amides were disclosed for both pharmacological activities (Figure 9.10). Compared to the phthalazines, putatively an internal H-bond keeps the two substituents in a comparable spatial arrangement. Extremely potent PDE5 inhibitors can be found in this class, e.g., 34 [40]. A similar internal H-bond can be speculated for 35, for which potent PDE5 inhibitory activity was likewise reported [41], Compound 36 represents the transition between phthalazines and anthranilic acid amides [42],... 

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