Description

Commercial Opportunity
A cellular screen has identified potent (< 100 nM) inhibitors of telomerase expression, which bind to novel targets in this pathway. CRT is seeking a commercial collaboration to progress the compounds with the view to offer an option for the exclusive licensing of these telomerase inhibitors.
 
Therapeutic Rationale
The end of linear chromosomes is formed by a special heterochromatic structure, known as the telomere. During cell cycle division telomeres shorten as a result of incomplete replication of DNA molecules by conventional DNA polymerases, a process known as telomere shortening which ultimately leads to senescence or apoptosis. Excessive telomere shortening can also trigger a DNA damage response at the chromosome ends, which are recognized as double strand breaks. Telomerase compensates for telomere shortening by synthesising telomeric DNA at chromosome ends. In human cells, the enzyme complex functions by the de novo addition of TTAGGG repeats by the reverse transcriptase catalytic subunit (hTERT) using an integral RNA component (hTR) as a template for synthesis.

Dysfunctional telomeres can be a source of genomic instability in highly proliferating pre-cancerous cells and can lead to cancer depending on the integrity of the cell’s DNA damage response.

Telomerase is encoded by a non-redundant gene and its expression is found in germline cells, but not in normal human somatic tissues. In cancer, one of the important tumour escape mechanisms is reactivation of telomerase expression via signal transduction pathways to circumvent cell mortality. Telomerase is expressed in > 85% of tumours from all types of cancer and its reactivation is thought to stabilise telomere length, compensating for telomere erosion and hence preventing senescence and apoptosis whilst providing unlimited proliferative capacity to malignant cells.

Inhibition of telomerase in tumour cells is an attractive anticancer therapy which should disrupt telomere maintenance in malignant cells leading them to proliferative crisis followed by senescence or cell death. Hanahan and Weinberg have recently identified inhibition of telomerase as one of the key therapeutic points to address one of the so called “hallmarks of cancer”.

Download the PDF of Small Molecule Inhibitors of Telomerase Expression

For more information please contact

Dr Tanya Moore

+44 (0) 20 3469 6300 .(JavaScript must be enabled to view this email address)