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Nuevos fármacos de bajo peso molecular para el tratamiento del cáncer y enfermedades inflamatorias y fibróticas

Resumen

Tipo:
Oferta Tecnológica
Referencia:
TOCH20170531001
Publicado:
12/06/2017
Caducidad:
12/06/2018
Resumen:
Una pyme suiza de biotecnología ha desarrollado inhibidores de bajo peso molecular de proteínas BET (bromodominio y dominio extraterminal). Estos compuestos tienen potencial para el tratamiento del cáncer y enfermedades inflamatorias y fibróticas, no son tóxicos prácticamente y son perfectamente tolerados por varias especies de animales. Los inhibidores se emplean combinados o como alternativa al tratamiento actual con componentes biológicos, y ofrecen la ventaja de reducir los costes de producción. La empresa busca socios con el fin de establecer acuerdos de licencia y cooperación en materia de investigación para desarrollar las moléculas.


Details

Tittle:
Novel small molecule drugs for treating cancer, inflammatory and fibrotic diseases
Summary:
A Swiss biotech SME developed small molecule inhibitors of Bromodomain and Extra-Terminal motif (BET) proteins. The compounds have potential for treatment of cancer, inflammatory and fibrotic diseases. They are relatively non-toxic and well tolerated in several animal species. They can be used in combination with or even as replacement of current treatment with biologics and have the advantage of much lower production costs. Licensing and research cooperation to develop the molecules is sought.
Description:
Recent research has demonstrated that transcriptional control of key genes involved in cancer (e.g. c-myc) and inflammation (e.g. interleukin beta, interleukin 6) is controlled by epigenetic modulation via histone acetylation/deactetylation. Bromodomain-containing proteins tightly bind to acetylated lysine residues in histones and other proteins, and thereby prevent access to histone deacetylases and so enable gene transcription. Displacement of BET-bromodomains from the acetyl- lysine residue can be achieved by small molecules fitting in the acetyl-lysine binding pocket, thus leading to prompt inhibition of transcription of the above-mentioned genes.

The Swiss SME has created novel compounds which potently inhibit BET-bromodomain protein 2-4 and potently suppress proliferation of various cancer cell lines (in particular leukemia and lymphoma cells). Their potential for treatment of inflammatory and fibrotic diseases is harboured by their ability to suppress expression of interleukin 6 by macrophages stimulated by lipopolysaccharide, of vascular cell adhesion molecule by endothelial cells and of CC-chemokine ligand 2 (also known as monocyte chemotactic protein 1) by astrocytes stimulated with tumor necrosis factor alpha.
Their potential as antifibrotic agents is illustrated by their ability to inhibit liver stellate cells to be transformed in myofibroblasts and to suppress expression of collagen and of smooth muscle actin by these cells after stimulation with transforming growth factor beta.

The SME is at this time working in virtual mode. Partnership is envisaged in the form of a research and development/licensing agreement, to generate candidates for clinical development, at which time the entity can be further financed by established investors or big pharma companies.


Advantages and Innovations:
The current compounds are potent (IC50 for cytokine inhibition in the nanomolar range) and relatively non-toxic in vitro (no loss of viability in concentrations up to 50 uM). They are well tolerated in several animal species after oral, intraperitoneal and subcutaneous administration in doses of up to 50 mg/kg.
They can be used in combination with or even as replacement of current treatment with biologics, and have the advantage of much lower production costs.
The compounds are patentable, easy to synthesize, and are amenable to further optimization.
Stage of Development:
Under development/lab tested
IPs:
Secret Know-how

Partner sought

Type and Role of Partner Sought:
The specific area of activity of the partner:
The partner sought at this time preferably is another SME or an R-Y-D institution interested in cancer, inflammatory and fibrotic diseases and is seeking to expand its preclinical pipeline.

The tasks to be performed by the partner sought:
The partner should have means to perform (or outsource) preclinical pharmacology and preclinical development ADME-Tox (absorption, distribution, metabolism, excretion and toxicity).

Client

Type and Size of Client:
Industry SME <= 10
Already Engaged in Trans-National Cooperation:
Si
Languages Spoken:
Dutch
English
German

Keywords

Technology Keywords:
06001003 Citología, cancerología, oncología
06001011 Enfermedades circulatorias y del corazón
03004007 Pharmaceutics
06001015 Productos farmacéuticos / medicamentos