Chaperones

An emerging concept for cancer treatment consists of targeting proteins that affect multiple pathways involved with the malignancy. In this category, there is the chaperone inhibition since these proteins contribute to the correct folding of a large number of key proteins involved in all the hallmarks of cancer, such as Raf-1, Akt, Cdk4, HIF-1, p53 and Bcr-Abl.

 

Crystax has successfully crystallised several members of the HSP family. These targets have been submitted to the B2D2™ platform which has allowed the design of several novel chemical series of chaperone inhibitors.

Chromatin Modifying Enzymes

Post-transcriptional modification of histones can regulate gene expression and, therefore, be involved in pathological processes. The epigenetics targets are raising interest due to its therapeutic potential. Histone Deacetylases and Histone Methyl Transferases are protein families directly involved in expression of genes and, therefore, attractive targets in oncology.

 

Several members of this family have been submitted to our B2D2™ platform and work is ongoing to evolve the identified fragment hits.

 

DNA bis-intercalators

DNA has been widely used as a target in oncology. Several intercalators are currently in clinical use as amsacrin, daunomycyn, epirubimcin, captotecine and an appreciable number of intercalators and bis-intercalators are in clinical trials. Based on a natural lead compound named cryptoleptine, Crystax has identified several bisintercalators, which are up to 20 times more potent than the natural compound.