At rngen, our Scientific Platform produces new, specific Systems Chemical Pharmacology Drugs (SCPD) targeting inflammation and oxidative stress. The compounds created have specific, but multiple mechanisms of action in complex disease pathologies.
The parent drug is both a substrate and inhibitor of a key enzyme in the disease. This initial enzyme metabolizes the parent drug to a reactive intermediate that subsequently inactivates other proximal pathway proteins key to the disease. A SCPD has a highly localized effect on multiple targets, leading to additive or synergistic mitigation of the disease.
Our platform generates lead compounds with specific SCPD pharmacophore features using computational drug design, integrated with proprietary bioassays, and In vivo animal disease models to efficiently identify and validate promising drug candidates. By combining advanced in silico modeling with rigorous experimental validation, we create first-in-class therapeutics that have the potential to transform patient outcomes.
The platform is based on the creation of first-in-class Systems Chemico-Pharmacology Drugs (SCPD) using a combination of AI mediated discovery and rapid assay determination of compounds for SCPD compounds. The drugs created have multiple mechanisms of action centered on key events in complex disease biology.
The parent drug is a substrate for and/or inhibitor of a key enzyme in the disease. The enzyme metabolizes the parent drug to a reactive intermediate that converts proteins key to the disease in the local environment to their inactive states. An SCPD therefore has a highly localized effect on multiple targets, leading to additive or synergistic influence on the disease.
This platform enables us to address the underlying causes of diseases and develop effective treatments. We are dedicated to advancing scientific knowledge and improving patient outcomes through our research efforts.
After determining if a compound is likely to be an SCPD candidate then further studies are performed. They consist of the following:
In Vitro Testing: Precision at the Cellular Level
Our drug discovery process begins with a high-throughput proprietary in vitro bioassay system tailored to measure key metabolomic, proteomic and cellomic responses linked to oxidative stress and inflammation. This proprietary system allows us to rapidly screen and refine drug candidates, assessing their ability to modulate critical pathways.
We also determine the required physicochemical properties: chemical makeup, stability, and solubility of the compounds. Agents passing those requirements are further evaluated in vitro with pharmacology experiments, including enzyme inhibition, individual cell-type dynamics, and systems pharmacology determinations.
Different routes of administration are examined to determine bioavailability in rodents. By leveraging a combination of enzymatic assays, cell-based models, and real-time analytical tools, we gain early insights into efficacy, toxicity, and mechanism of action before advancing to preclinical models.
In Vivo Validation: Translating Science into Therapeutics
Once a candidate demonstrates strong potential in vitro, it undergoes rigorous In vivo evaluation using well-established disease-relevant animal models. These models enable us to study drug distribution, pharmacokinetics, and therapeutic effects in complex biological systems.
We employ state-of-the-art imaging, biomarker analysis, and behavioral assessments to confirm efficacy and optimize dosing. This multi-tiered approach ensures that only the most promising SCPD candidates advance toward clinical development, maximizing both safety and therapeutic impact.
In vivo pharmacodynamics via the route(s) of administration defined above of the lead agents are evaluated in rodents and rabbits. We have examined KYC in animal models of bronchopulmonary dysplasia (BPD), sickle cell disease (SCD), relapsing remitting multiple sclerosis (RRMS), ischemic stroke, and traumatic brain injury/chronic traumatic encephalopathy (TBI/CTE).
The in vivo pharmacokinetics are determined in rodents. Agents that pass the requirements in all of the above experiments are then scaled up in production. The chemical manufacturing process is then performed. For example, this has been done for KYC acetate wherein 7.5 kg was produced at extremely high purity, and its stability has been studied for over a year. In vivo toxicology, which requires a large amount of the agent, is then determined.
The FDA usually requires safety testing in at least two mammalian species, one non-rodent, prior to authorization for human trials. We have examined the toxicology of KYC in rats by different routes of administration. Organs targeted by the drug and any long-term toxic effects are presently under study. Along with the toxicology, the in vivo toxicokinetics in rats have also been performed.
Once the toxicology/toxicokinetics experiments in rats are complete, we will translate the findings to similar studies in dogs. The data from the experiments above will allow us to allometrically estimate a safe starting dose of our drugs for clinical trials in humans.