SA.41471(2015/X) Purpose_public_aid: Article 25 of Regulation (EC) No 651/2014 of 17 June 2014 declaring certain categories of aid compatible with the internal market in application of Articles 107 and 108 of the Treaty (OJ Urz. EU L 187/1 of 26.06.2014).The search for strategies to selectively eliminate cancer cells is important for improving the effectiveness and safety of cancer therapy. One of the innovative approaches is to use the so-called synthetic lethality phenomenon. It is based on observation that simultaneous mutations of some gene pairs can lead to cell death, while damage to each individual does not produce a lethal effect. The aim of the PROJECT is to implement into the activities of Ryv, a candidate for a drug at stage I of the clinical phase with a mechanism of action, based on the phenomenon of synthetic lethargy. The drug will only show anticancer efficacy in the presence of mutations, causing synthetic lethal phenotype. The therapeutic indication will be selected tumours in which treatment methods are highly ineffective. By means of bioinformatic research and cellular models, Ryvu identified and confirmed new synthetic lethal relationships. The results were used in the design of original helicase strategies as a class of therapeutic proteins: •The first goal is BRM helicase, which is part of the complex regulating the status of SWI/SNF chromatin. The frequency of mutations in the subunits of the complex is very high and is 20 % of solid tumours (Kadoch et al.2013). •The second goal is WRN helicosis involved in the replication, repair and maintenance of genome stability. The screening tests selected the first active substances. Their validation and intensive chemical development allowed to obtain substances with improved physico-chemical parameters, activity and ADME.[...]