Noxi Lab is a technological unit of Gurus which develops a nitric oxide-donating research platform to generate innovative drugs, pharmaceutical substance hybridization technology which uses biologically active linkers and other modern technologies
The current problem of the industry
Dominating concept of "magic bullet", which was proposed more than 100 years ago by Paul Ehrlich and based on "one drug - one target - one disease" philosophy does not permit to make a significant leap in the therapeutic approaches. Monofunctional compound should be regarded as designed to act on a single, well-defined biological target. Modern monofunctional compounds are designed by using computer modeling and molecular docking methods to achieve maximum complementarity of the designed compound and the active site of the biological target. Created as monofunctional drugs, they mostly are perceived as xenobiotics by the human body, and to overcome the resistance of the body is necessary to significantly increase the dose of the drug, often not achieving the desired therapeutic result and increasing the risks of complications.
Accordingly, the multi-functional compound is capable to act at two or more biological targets and work on a several active mechanisms of pathology simultaneously for a comprehensive regulatory impact. Wherein the risk of complications is minimal compared to monofunctional compounds.
Significant limitations of monofunctional drugs became clear in the last decade, when a sufficient number of these drugs have been withdrawn from the market or clinical trials were terminated. At the same time the industry came to an understanding of complexity and comprehensiveness of chronic diseases. This cleared the necessity to replace the paradigm of multi-functional "magic bullets" that affect one specific target to paradigm polypharmacology assuming simultaneous action on many targets. Such effects can be achieved by:
a) a simultaneous administration of several monofunctional drugs that is widely practiced today by physicians and already recognized as ineffective;
b) a mixing of two active pharmacological ingredients (APIs) in a single formulation, that only partly overcomes the limitations of monofunctional drugs;
c) using the rational design of multifunctional drugs on the principle of "one drug - many targets".
Our technology as an alternative solution
We have developed a research platform based on distributed regulatory impact concept. Our research platform allows synthesizing hybrid multifunctional compounds in line with "one drug - many targets" principle. Such substances have a complex regulating influence on active pathological processes. One of the most successful candidates for the synthesis of multifunctional hybrid compounds is a nitric oxide (NO) which is a gaseous signaling molecule or gasotransmitter. The presence of NO-releasing moiety in hybrid molecule gives it new properties due to involvement in the pharmacological effect the physiological mechanisms activated by NO with simultaneous compensation of nitric oxide insufficiency that accompanies many pathological conditions. This greatly increases and expands the effectiveness and pharmacological potential of the new molecule. Thus true multifunctionality arises in hybrid molecules which get an opportunity to act complexly at the complicated mechanism of the pathological process through impact on several key targets. Based on the concept, we have developed the original technological platform that includes a unique technology of various nitric oxide donors’ synthesis, methods of their introduction in pharmacophores of natural origin (endogenous bioregulators) and APIs of known drugs. Multifunctional hybrid molecules generated by NO-donating platform showed in experiments higher pharmacological activity than the sum of their individual components.
The advantages of multifunctional drugs
• High efficiency due to complex action at the different pathogenic pathways.
• Excellent safety profile caused by maximal usage of endogenous molecules, which significantly reduces the risk of undesired side effects and complications.