Targets addressable by polyketides
Polyketides offer particular potential in areas difficult for traditional small molecules
Functional ‘themes’
Polyketides often commonly show activity in certain functional themes that take advantage of their molecular size and complexity. These include:
- Protein assemblies (e.g. spliceosome; proteasome): polyketides often inhibit protein:protein interactions
- Stem cell differentiation
- ‘Gain-of-function’ – polyketides can bring together protein partners that would not be associated in nature to produce a therapeutic effect (e.g. rapamycin; FK506)
- Signalling pathways
Target classes
Polyketides interact with a broad range of target classes, many of which are difficult to access with conventional small molecules. These include:
- Protein:protein interactions (e.g. spliceosome; proteasome)
- Chaperones and foldases (e.g. Hsp90; FKBPs; cyclophilins)
- Transcription factors
- Transporters (e.g. CRM1, glucose-6-phosphate transporter)
- Kinases; phosphatases; ATPases
- Topoisomerases; HDACs
- tRNA synthetases
- Ion channels
