Success Stories

To demonstrate our expertise, some selected projects which were recently carried out successfully are summerized here.

Development of inhibitors of transketolase TKTL1 - a new target for cancer diagnosis and therapy

Since 2006 ElexoPharm in  cooperation with a medium sized pharmaceutical company is involved in a research project dealing with the design and development of new anti cancer drugs.
The discovery and identification of a novel biological target, the enzyme transketolase-like 1(TKTL1), opened new promising chances in the field of cancer research. The enzyme TKTL1 is strongly expressed in aggressive tumor cells, which are resistant against chemotherapeutics.
The aim of the research cooperation between the medium sized pharmceutical company and ElexoPharm is an efficient design of lead compounds, highly potent TKTL1 inhibitors, which show selectivity towards other transketolase enzymes. The complementary expertise of both companies guarantees a quick and efficient success.

Development of a 3-D model for hepatic drug toxicity

The ElexoPharm GmbH is partner in project funded by the German Ministry for Education and Research, dealing with the development of a three dimensional model for the prediction of hepatic drug toxicity. To validate this model it is necessary to determine the metabolic profile of known drugs. The metabolites which are not commercially available will be synthesised by ElexoPharm scientists using modern organic synthesis techniques. The aim of the project is to develop a model which is closer to the human in vivo conditions than the currently used two dimensional in vitro test systems. This may lead to a further reduction of animal tests.

Development of highly selective and highly potent inhibitors of aldosterone synthase (CYP11B2) for the treatment of cardiovascular diseases like congestive heart failure and myocardial fibrosis

After identification of aldosterone synthase (CYP11B2) as drugable target by Hartmann et al. first hit compounds were optimised to early lead compounds using a several assay containing in vitro test system.
Within a few months two early lead compounds have been optimised in terms of potency and selectivity by rational drug design using modern medicinal chemistry methods (analysis of structure activity relationships, docking studies, synthetic introduction of suitable substituents in selected positions of the molecule). In summary, after the synthesis of only 350 compounds the selectivity towards the 95% homological enzyme CYP11B1 was successfully increased to a factor of 1000. The selectivity towards the most important hepatic CYP enzymes is outstanding and the pharmacokinetic profile shows very good bioavailability and satisfactory half life times.

Development of highly selective and highly potent inhibitors of 17beta-hydroxy steroid dehydrogenase 1 for the treatment of estrogen dependent diseases like breast cancer and endometriosis

17β-Hydroxy steroid dehydrogenase 1 has been recognised to be a suitable target for the treatment of estrogen dependent diseases like endometriosis and breast cancer. First examinations by Hartmann et al. revealed early lead compounds. An in vitro test system for high throughput screening at human 17β HSD1 as well as in vitro tests for 17β HSD2 and for the affinity to ERα and β have been successfully established for the in house determination of the selectivity towards these enzymes.
Although several X-ray structures of 17β HSD1 were available, "tailored" compounds were only poorly active, suggesting that the binding mode of non steroidal compounds differs from that of the steroidal substrate estron. Intensive studies of structure activity relationships and molecular modelling experiments lead us to possible compounds of different substance classes, which were synthesised by highly experienced and skilful synthetic chemists in shortest time. After the synthesis of only 200 compounds we obtained leads that show very high potency (IC50 in the low nanomolar range) and are highly selective. The selectivity towards hepatic CYP enzymes is outstanding and the pharmacokinetic data are very promising.