Di- and Triphosphate prodrugs with controlled release mechanism
We are presenting a new therapeutic family of components to fight a number viral infections and tumor tissues. Through a remarkably modulable synthesis we are able to create nucleoside derivatives with variable lipophilicity and stability in the cell. Our masked nucleosides are highly selective to viral polymerases, sinking the toxicity risk of their application.
Nucleoside analogues are extensively used as agents in antiviral and antitumour therapies.
Their biological activity is regulated by kinases through the control of the mono-, di- and triphosphate derivatives. This catalytic effect is, however, suboptimal, so that their effect is masked.
We introduce a new and very flexible prodrug concept to circumvent the limitations of current therapies and offer a new approach for a wide range of chemotherapeutics.
Bilder & Videos
Our approach effectively introduces a multiple and flexible masking of the nucleoside di- or triphosphates.
The masking enables an enzyme-driven hydrolytic process that leads to the selective release of any di- or triphosphate inside target cells.
In order to implement this approach, a unique synthesis route was experimentally developed. A significant variety of masks with a very high conversion factor has been produced in a high purity and yield. This allows the modulation of the stability and the cell permeability of the active ingredient.
We offer a family of active ingredients with remarkable advantages in its main applications:
- Tumour treatment: As proven through in vitro tests, the active ingredient penetrates into the tumour tissue, also in solid tumours. This solves a common problem of current chemotherapy agents.
- Antiviral treatment: The nucleotide derivative is selectively recognised by viral polymerases. Toxicity to cellular polymerases has not been observed.
- HCV: In-vivo tests on mouse model have shown excellent results, concerning the absorption of the active ingredient. When applying this concept to a reference, nucleoside-based HCV virostatic the amount of active substance found in the liver was twice as high as by administering the commercial drug Sofosbuvir.
Our approach addresses the required formation of di- and triphosphates starting from a lipophilic prodrug that ensures the active ingredient crosses the cellular membrane.
Different modifications of the nucleosides lead to modulable lipophilicity and stability in the cytosol.
This solution offers remarkable advantages:
- Controlled release mechanism
- Controllable lipophilicity
- Controllable stability
- Antiviral & antitumoural effect
- Higher catabolic stability
- Enhanced selectivity to viral polymerases
- Virostatics (HIV, HCV, Influenza)
- Antitumoral drugs
- R&D Cooperation
- Transfer of rights
Publikationen & Verweise
Lipophilic prodrugs of nucleoside triphosphates as biochemical probes and potential antivirals
Nature Communications 6, 8716, 2015, doi:10.1038/ncomms9716
Weitere Information zum Herunterladen
- 140 Ki
- PCT PCT/DE2015/200440 anhängig
StichworteNucleotide Prodrugs, Nucleotide analogues, Modulable nucleoside masking, Tunable lipophilicity & stability