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Development of synthesis, analysis, and asmf of leakadin, an anticancer and autoimmune disease treating substance

An international collaboration between three companies will develop the active substance drug master file (asmf) of an original medication leakadin according to eu standards. The main project aim is to develop micro reactor technology for its chemical synthesis.

Oncologic and autoimmune diseases are the second most widespread cause of death after cardiovascular diseases in economically developed regions such as the European Union and North America [Statistics of the World Health Organisation (WHO)]. Moreover, the WHO anticipates a vast increase in oncologic diseases by 2025 given the clear ageing trends in the EU and North America. However, customers from economically developed regions consume up to 85 % of the total world drug market, which made 580 billion US dollars in 2006. In light of these facts, the pharmacological industry is actively working on anticancer drugs. For instance, 54% of all 7 200 active projects directed towards new medicines in 2006 were intended for anticancer substances. Nonetheless, different anomalies of the human immune system are not always at the centre of active pharmacological research. Thus for the treatment of psoriasis and Lupus erythematosus, drugs developed 5-7 years ago are still used. It should be pointed out that psoriasis treatment with such common corticosteroid and systemic immunotoxic drugs as methotrexate, cyclophosphamide, and aritinine statistically increases morbidity with diabetes and rheumatoid arthritis. In the 1970s and 1980s, there were active research projects in GERMANY (Boehringer Ingelheim) and LATVIA (Latvian Institute of Organic Synthesis, LIOS) directed towards aziridine scaffolds in order to establish their alkylating ability in the context of anticancer studies. In the late 1970s, BOEHRINGER INGELHEIM stopped their investigations on Imexon as it did not show enhanced alkylation of nucleic acids when compared with products already known at that time - cyclophosphamide, treosulfane and others. However, projects dealing with the development of Leakadin continued with good results in oncologic centres in LATVIA, UKRAINE and RUSSIA until mid-1990s. The mechanism of Leakadin action is still not completely understood, however, empirical results obtained in clinical studies on cancer patients (multiple myeloma, pancreatic adenocarcinoma, malignant melanoma) and patients suffering from autoimmune diseases (psoriasis, Lupus erythematosus, rheumatoid arthritis) allowed for the following hypotheses: - Leakadin binds with thiol groups of cancer cell membrane proteins. Such 'leakadinated' cells become targets for the immune system of the organism and thus are destroyed. - Leakadin normalises the ratio between subpopulations of T-lymphocytes (T-helpers and T-suppressors). The latter results in a normalised chain process of the immune system, which leads to decreased amounts of autologous antibodies synthesised by B-lymphocytes (autologous antibodies act against cells of mucous membranes and skin of the organism itself.) In light of these facts, Leakadin can be attributed to the group of weakly alkylating and immune stimulating anticancer substances. The use of it prolongs the survival of cancer patients and enhances their life quality. This perfectly corresponds to the latest opinions on treatment where early diagnostics of cancer are combined with the administration of immune stimulating medicine. The long-term project goal is to renew the use of Leakadin for the treatment of certain types of cancer and autoimmune diseases (psoriasis, Lupus erythematosus). The plan is to register it and to direct the registered drug to its historic markets of RUSSIA and other countries of the former Soviet Union as well as to penetrate the markets of the EU. The ultimate objective of the first 16 months (phase I) of the project is to develop a synthetic technology for industrial production of the active drug substance of Leakadin - aziridine carboxamide. To make it economically feasible and environmentally friendly we plan to adopt the latest developments in science and technology and namely the use of micro-reactors. The results of phase I of this project will be a patent for Leakadin synthesis technology and an Active Substance Drug Master File, which is a package of registration documentation in line with EU standards.
Acronym: 
LEAKADIN ASMF
Project ID: 
4 161
Start date: 
01-04-2008
Project Duration: 
16months
Project costs: 
250 000.00€
Technological Area: 
Pharmaceutical Products / Drugs
Market Area: 
Pharmaceuticals/fine chemicals

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