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H2020: Búsqueda de instituto de investigación o universidad para participar en una propuesta sobre sustitución de insulina con nuevos metalofármacos que presentan actividad insulinomimética


Búsqueda de socios
El laboratorio de química inorgánica de una universidad griega especializado en actividad insulinomimética busca socios con el fin de preparar una propuesta para comprender los mecanismos moleculares de nuevos metalofármacos que presentan actividad insulinomimética. El laboratorio busca un instituto de investigación o una universidad con experiencia en investigación del síndrome metabólico para presentar la propuesta a la convocatoria H2020-SC1-PM-09-2016 (Nuevas terapias para enfermedades crónicas). La fecha límite de la convocatoria es el 13 de abril de 2016 y el plazo para presentar expresiones de interés finaliza el 29 de febrero.


H2020: Research institute or university requested to participate in a proposal regarding substitution of insulin with novel metallodrugs exhibiting insulinomimetic activity.
The laboratory of inorganic chemistry of a Greek university, which is active in insulin mimetic activity is looking for partners to set up a proposal regarding the understanding of the molecular mechanisms of novel metallodrugs exhibiting insulinomimetic activity. They are looking for a research institute or university with expertise in metabolic syndrome research in order to submit a proposal to the call H2020-SC1-PM-09-2016: New therapies for chronic diseases.
Diabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia due to the absence of insulin or to impaired insulin secretion. Overcoming severe problems associated with the nature and administration of currently employed drugs in the treatment of the two types of DM (I and II) constitutes a contemporary challenge in research and in the pharmaceutical industry.

Driven by the need for novel drugs exhibiting atoxic cellular behavior, adipogenicity and insulin enhancing action, the laboratory of inorganic chemistry of this Greek university has selected specific metal ions to guide the design and synthesis of such pharmaceutical materials. The selection and design was based on the fact that among the various roles of vanadium V(V), zinc Zn(II) and chromium Cr(III) discovered to date, their exogenous activity as insulin mimetic agents stands as a contemporary challenge currently under investigation and a goal to pursue in the form of metallodrugs against type 2 Diabetes Mellitus (chromium supplements have tacitly started emerging in the pharmaceutical market).

Within this context, the laboratory has already performed a preliminary study in order to investigate the adipogenic potential of Zn(II), V(V) and Cr(III) and appropriately configure their coordination sphere into well-defined anti-diabetic forms. In particular:-

a) a series of new well-defined ternary dinuclear M-L (M= Zn(II), V(V) and Cr(III); L = Schiff base ligands with a variable number of alcoholic moieties, other natural organic substrates) compounds were synthesized and physicochemically characterized
b) their cytotoxicity and migration effects in both pre- and mature adipocytes was assessed,
c) their ability to effectively induce cell differentiation of 3T3-L1 pre-adipocytes into mature adipocytes was established, and
d) closely-linked molecular targets involving or influenced by the specific Zn(II), V(V) and Cr(III) forms were perused through molecular biological techniques, cumulatively delineating factors involved in metal-induced adipogenesis.

Collectively, the results:-
a) reveal the structural selection of bioactive metallodrug forms, exemplifying the significance of key structural features of organic substrates-ligands coordinated to Zn(II), V(V) and Cr(III), thereby influencing its a) toxicity behavior and insulin-like activity,
b) project molecular targets influenced by the specific forms of Zn(II), V(V) and Cr(III) formulating its adipogenic potential, and
c) exemplify the interwoven relationship between (Zn(II), V(V) and Cr(III))-L structural speciation and insulin mimetic biological activity, thereby suggesting ways of fine-tuning structure-specific metal-induced adipogenicity in future efficient antidiabetic drugs.

To better understand these molecular mechanisms, the laboratory is currently preparing a proposal to be submitted under the call H2020-SC1-PM-09-2016: New therapies for chronic diseases. The relevant work program is published in draft. It is expected to open on 20 October 2015. The deadline for the submission of the proposal is 13 April 2016. The deadline for submission of Expressions of Interest is 29 February 2016.

The Greek laboratory is looking for a partner university or research institution with expertise in metabolic syndrome research. They are already in discussion with other research organisations with particular expertise and a pharmaceutical company in order to complete the consortium.
Advantages and Innovations:
Metal-containing pharmaceuticals have been established over the past century and are currently being used to treat other diseases. In particular for the treatment of Diabetes Mellitus (DM) II, metallodrugs have the following advantages:-

1. They overcome insulin resistance and enhance insulin action.
2. They are novel anti-diabetic agents based on endogenous and naturally-occurring metal ionic species of adipogenic potential and glucose catabolism. Endogenous and exogenous metal ionic factors have been shown to enhance physiological processes linked to cellular aberrations (in a number of diseases).
3. Well-defined metallodrugs are atoxically, chemically and biologically suitable to overcome specific problems with insulin-linked glucose metabolism.
4. They can provide a structure-specific assessment of insulin-like effects in insulin sensitive tissues, which is the key to glucose uptake.
5. They show mechanistic delineation of insulin mimetic action.

Stage of Development:
Proposal under development
Technical Specification or Expertise Sought:
Proposals should focus on clinical trial(s), supporting proof of concept of clinical safety and efficacy in humans of novel therapies (pharmacological as well as nonpharmacological) or the optimisation of available therapies (e.g. repurposing) for chronic noncommunicable or chronic infectious diseases. Preclinical research should be completed before the start of the project. Proposals should provide a sound feasibility assessment, justified by available publications or provided preliminary results.

Partner sought

Partner Sought:
Type of partner: university or research institution Activity of the partner: metabolic syndrome research Role of the partner: Complete design, synthesis and physicochemical characterization of novel binary and ternary vanadium, zinc and chromium biomaterials with natural organic substrates. Determination of adipogenic capacity of zinc and vanadium species. Insulin enhancing action by chromium (Cr(III)). Diverse and extensive biological screening (toxicity, migration, lipogenesis, etc.). Assessment of tissue-specific molecular biomarkers, key to glucose uptake and metabolism.
Type of Partnership Considered:


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Evaluation Scheme:
Proposals must be submitted by the coordinator on-line via the Electronic Submission Service of the Participant Portal and before the call deadline. The evaluation of proposals will be carried out within one month of that date
Coordinator Required:
Deadline for Call:
Project Duration: