Neogalfarma
YEARS
2016 - 2018
Industry of application
Health
CALL
CONECTA-PEME-2016 (GAIN-Xunta de Galicia)
DESCRIPTION
The main objective of the project was the search for new drugs for cancer treatment through the development of therapies with different therapeutic targets and combined treatments. This was achieve through the following specific objectives:
- Develop new androgen receptor antagonists that are effective in animal models of prostate cancer and nominate a preclinical candidate.
- Develop new modulators of protein-protein interactions of the Bcl-2 family that are effective in animal models of cancer.
- Discover new inhibitors of the ALK5 kinase (Activin receptor-Like Kinase) and the TGF-beta signaling pathway that are effective in animal models of cancer.
- Discover new JAK kinase (Janus Kinase) inhibitors that are effective in animal models of myeloproliferative, hematological diseases or solid tumors.
- Development of new types of nanomaterials that present antitumor activity with low toxicity and/or that enhance the action of antitumor drugs directed against DNA.
- Study the synergy of these different mechanisms of action to treat various types of cancers in vitro and in vivo.
- Develop highly selective and sensitive analysis methods based on mass spectrometry coupled to liquid chromatography, which allow measuring the concentrations of the developed chemical compounds and their metabolites both in plasma and in tumors. In addition, biomarkers will be identified by applying proteomics techniques and tools based on high-resolution mass spectrometry.
The project ended with great success, completing the following milestones:
- Potent and patentable inhibitors of ALK5 have been identified. The pharmacokinetic properties of the best ALK5 inhibitors identified have been characterized.
- A series of GI-restricted JAK3/TYK2 inhibitors for the IBD-fibrosis-colon cancer axis have been developed and patented, active in a murine model of colitis and which do not present toxicity at high doses. These products are about to begin their first clinical study at the Sant Pau Hospital in Barcelona.
- A series of systemic JAK3/TYK2 inhibitors have been developed and patented for psoriasis. These products are powerful and selective, and their properties make them especially interesting for oral and topical treatment.
- A series of AR+GR antagonists have been developed and patented for prostate cancer that could enhance current enzalutamide treatments.
- Non-steroidal GR antagonists have been identified as activators of the immune system with potential for the treatment of colon cancer.
- A potential synergy of ALK5 inhibitors discovered by GalChimia with JAK antagonists discovered by Oncostellae has been identified.
- An efficient method for the synthesis of M-M (metal molecules or AQCs) of different sizes has been successfully developed.
- It has been proven that smaller M-M increase the accessibility of chromatin in proliferating cells, enhancing the effect of drugs whose target is DNA, so they could improve the effectiveness of current treatments.
- It has been proven that larger M-M have the ability to cross the blood-brain barrier to reach and reduce metastases, constituting an innovative tool to solve two of the main problems in cancer treatment.
- Highly selective and sensitive analysis methods based on HPLC-MS have been developed to measure the concentrations of the developed chemical compounds and their metabolites, both in plasma and in tumor.
- Biomarkers have been identified by applying proteomics techniques and tools based on high-resolution mass spectrometry.
Funding info
This project has been funded by Xunta de Galicia and the European Union FEDER (Operative Program FEDER GALICIA 2014-2020) through the subprogramme CONECTA PEME-2016, under the grant agreement IN852A 2016/2.
Consortium members
- AMSLab
- Galchimia
- Nanogap
- Oncostellae