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Nuevos compuestos patentados de primera clase que unen dos objetivos epigenéticos (metiltransferasas), más eficaces que los compuestos epigenéticos de referencia vs diferentes líneas celulares del cáncer


Oferta Tecnológica
Un centro de investigación español ha desarrollado moléculas pequeñas de primera clase dirigidas a dos objetivos epigenéticos (metiltransferasas). Las moléculas muestran una mayor eficacia en un rango de nm bajo contra líneas celulares de distintos tipos de cáncer (tanto tumores hematológicos como sólidos) en los que están implicados los objetivos epigenéticos. El modo de acción se valida en líneas celulares e in vivo. Se buscan socios académicos y empresas biofarmacéuticas con el fin de establecer acuerdos de cooperación en I+D, licencia, etc.


First-in-class novel proprietary compounds binding two epigenetic targets (methyltransferases), more effective than reference epigenetic compounds vs different cancer cell lines.
A private Spanish Research Center has developed first-in-class small molecules hitting two epigenetic metyltranferases targets. Proprietary molecules show improved efficacy at low nM range against cell lines from different cancer types (both haematological and solid tumours) where the epigenetic targets addressed are implied. Mode of action is validated in cell lines and in vivo. The Center is open to partnerships (R-Y-D cooperation, licensing...) with academia and biopharmaceutical companies.
A Spanish Research Center combines solid basic biology science with early preclinical drug development capabilities within a context of clinical patient care, oriented to solve medical problems for the benefit of the patient and the society.

The Center has facilities and processes for target-based and phenotypic drug discovery and early development of new therapeutic agents, up to the lead optimization stage. Noteworthy are: collection of biological samples; animal facilities, which include from knock-out mice to larger species; genomics, proteomics and bioinformatics unit; imaging unit, providing services of microscopy, non-invasive image acquisition of laboratory animals and quantitative image analysis.

Strategic linkage with the University Hospital enables and promotes the bidirectional flow of ´bench-to-bed´ knowledge and backwards.

Conscious of the complexity of this endeavor, the Center operates in a context of Open Innovation and collaborates with other research institutions, biotechnology and pharmaceutical companies, public institutions and investors.

Proprietary compounds:
Proprietary molecules bind two epigenetic targets and show an increase efficacy than reference epigenetic compounds versus different cancer cell lines. They show low nM efficacy (GI50<150 nM) against cell lines from different cancer types; for example, hematological (ALL or/and ABC-DLBCL) and solid tumors (bladder, hepatocelullar carcinoma, glioblastoma or/and melanoma).

Therapeutic Scope:
Epigenetic modifications are a major driver of biological complexity and can have a role in the development of a variety of disease treatments.
Epigenetics is an emerging area covering a broad range of mode of actions. However, only four drugs are currently approved and eleven agents are in early-stage trials.

Opportunity and Competitive Landscape:
- The fact that the epigenome is dynamic is of particular relevance to drug development, as it implies that specific disease-associated epigenetic states may be reversible with treatment.
- To date, the most investigated therapeutic area in terms of epigenetics is cancer.
- Beyond cancer, epigenetic factors have been implicated in inflammatory, autoimmune, metabolic, neurological and cardiovascular disorders.
- Four drugs with epigenetic mechanisms of action are currently approved. All of them are anticancer drugs and they are only focused on 2 modes of action (HDACs and DNMT-irreversible).
-Mostly, research is focused on developing novel HDAC inhibitors.

Indication: cancer, a wide range of neoplastic diseases in where the epigenetic targets addressed are implied.

Multifactorial optimization process, from initial proprietary hits to lead compounds:
- Hitting two independent targets at low nM range (IC50<100nM).
- In-vitro efficacy in cellular assays: epigenetic marks (EC50) and proliferation (GI50), both at low nM range.
- Optimal solubility, P450s profiling, hERG and plasma protein binding (unbound fraction).
- Cellular permeability. There is still room for improvement.
- Therapeutic window, efficacy vs toxicity, just >1 log unit (to be improved).
- Acceptable pharmacokinetics.
- In vivo proof-of-concept.

Validation process: Chemical probes were discovered and utilized for in-vitro cellular Proof-of-Concept (PoC).
- Functional response. These proprietary molecules impact on the corresponding epigenetic marks (EC50) and inhibit proliferation of cancer cell lines (GI50).

Lead compound, CM-272, was tested in vivo efficacy study:
- Mice inoculated with ALL CEMO-1 cell line, hematologic cancer, were treated with CM-272 (2.5 mg/Kg, i.v.) for 28 days. These mice showed a significant increase in survival probability compared to untreated animals (untreated 70 days vs treated 100 days; p=0,0009).

The Center is open to a range of partnerships (R-Y-D cooperation, financing, joint venture, licensing) with academia and biopharmaceutical companies interested in further development.
Advantages and Innovations:
First-in-class. Novel methyltransferase mode of action has been identified and validated.
Dual and reversible inhibitors against two epigenetic target classes.
Stage of Development:
Available for demonstration
Patent(s) applied for but not yet granted

Partner sought

Type and Role of Partner Sought:
- Type of partner sought: academia, biopharmaceutical companies.
- Specific area of activity of the partner: Medicine.
- Task to be performed: To facilitate the advancement of the research, with the ultimate goal of improving patient quality of life. By joining capabilities and resources, this win-win cooperation facilitates the advancement in the different research stages, from target validation to lead optimization or early candidate development.


Type and Size of Client:
R&D Institution
Already Engaged in Trans-National Cooperation:
Languages Spoken:


Technology Keywords:
06001003 Citología, cancerología, oncología
06001015 Productos farmacéuticos / medicamentos