| Α/Α | Work package 1 (WP1) |
|---|---|
| Title of WP | Design and synthesis of products |
| Activity Category | Industrial Research under Conditions |
| Responsible Body | DCUP, Department of Chemistry, University of Patras (Body 2) |
Objectives of WP1
The aim of WP1 is the synthesis and identification of GnRH peptide analogues conjugated with cytostatic compound as well as the determination of the physicochemical properties of the synthesized compounds.
Summary of WP1
The Key activities of WP1 are:
- Design – Synthesis of compounds: Peptide analogues of GnRH will be synthesized, to which a thiol group will have been added to the side group of the amino acid at position 6 of the peptide backbone, as it is necessary for the formation of the disulfide bond. The purification and identification of the synthesized compounds will be performed by High Performance Reverse Phase Chromatography (RP-HPLC) and Electron Spray Ionization Mass Spectrometry (ESI-MS). Moreover, before the evaluation of the analogues, the presence of endotoxins will be checked (creation of sterile samples).
- Determination of Physicochemical properties and stability of synthetic products: The study will be carried out according to international standards. An analytical method using High Performance Liquid Chromatography (HPLC) and/or a spectrophotometric method and/or other equivalent method, will be used to carry out the research.
- Website construction and maintenance: The site will aim to provide information about the project, the scientific and technical idea.
| Α/Α | Work package 2 (WP2) | |
|---|---|---|
| Ιn vitro evaluation of synthesized compounds | ||
| Activity Category | Industrial Research under Conditions | |
| Responsible Body | DCUP, Department of Chemistry, University of Patras (Body 2) | |
| Collaborate bodies | Body 2 (DCUP) | LFUK, Laboratory of Pharmacology, University of Crete (Body 3) |
Objectives of WP2
The aim of the WP2 is the in vitro evaluation of the synthesized compounds and includes: (i) Determination of the anticancer activity of the synthesized products in human breast, endometrial and prostate cancer cell lines that the GnRH receptor is expressed; (ii) Pharmacological evaluation: binding studies, receptor endocytosis and cellular signaling, using HEK 293 that heterologously expresses the GnRH receptor; (iii) Control of disulfide bond cleavage by the use of the thioredoxin system; (iv) Control of the entry of the cytostatic compound into the cell; and (v) Study and identification of cancer cell killing mechanisms.
Summary of WP2
The Key activities of WP2 for the in vitro evaluation of the synthesized compounds includes:
- Binding studies
- Signaling studies
- Endocytosis studies
- Anticancer activity studies in various human cancer cell lines – Mechanism of cell killing
The most bioactive products will be selected, which will then be tested for their in vivo activity in the WP3.
| Α/Α | Work package 3 (WP3) |
|---|---|
| Title of WP | In vivo evaluation of the most active synthesized compounds |
| Activity Category | Industrial Research under Conditions |
| Responsible Body | LFUK, Laboratory of Pharmacology, University of Crete (Body 3) |
Objectives of WP3
The aim of WP3 is the in vivo evaluation (proof of concept) will be performed with the most bioactive compounds that will emerge from the WP2.
Summary of WP3
The research procedures for the in vivo evaluation will be approved by the Veterinary Service of Crete and the Animal Standards Committee of the Medical School of the University of Crete.
The results of the pre-clinical evaluation will be described in the Technical Feasibility Study – Business Plan (see EU 4) which will be the basis for the utilization of the most active final product.
| Α/Α | Work package 4 (WP4) |
|---|---|
| Title of WP | Technical Feasibility Study – Business Plan |
| Activity Category | Industrial Research under Conditions |
| Responsible Body | 1 (Excelya, former ZeinCRO) |
Objectives of WP4
The aim of WP3 is the creation of a Technical Feasibility Study (TFS) and Business Plan.
Summary of WP4
Creation of a Technical Feasibility Study: The Technical Feasibility Study (TFS) will record and identify in an objective and rational manner the advantages, the possible problems of execution and how to deal with them, the resources required for the implementation of the project, and the strategies that will ensure the sustainability of the results. after its implementation.