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- Phenotype Identification - Chromatographic Separation - Spectroscopic Characterization - Structure Elucidation - Assay Validation - Metabolite Generation & Qualification - Attenuation / Suppression Modulation - Genotoxicity, Teratology Evaluation - Drug Interaction Quantification - Phenotype Stratification - Metabolism Prediction - Dose Response Analysis - Pathway Postulation & Confirmation - Dose Regimen Modification
- NCE Discovery / Prioritization - Optimized Dosing Regimens - Comparative Drug Safety - Patient Diagnosis & Treatment - Prediction of Synergistic Drug Administration
Few mechanisms exist to predict and quantify the accurate formation of metabolites and their likely clinical impact. This is an issue when multiple drugs are administered, resulting in lower efficacy and/or adverse reactions due to drug-to-drug interactions. Pharmacologists do not know, in advance, the structure of the metabolites they should seek. Metabolites of several drugs have not been comprehensibly identified and many of the metabolites are not amenable to organic synthesis by facile routes. The current process for detecting metabolites involves animal studies, painstaking isolation from bodily fluids, and laborious synthesis.
Liver slice preparations are of variable potency and it is difficult to quantitate the precise stoichiometry
of the oxidant.
The metabolites generated using current methods are not produced in the adequate quantities
needed to correlate with clinical data, refine clinical protocols or design new chemical entities.
Since the metabolic processes in vivo contribute in substantial measure to the efficacy, side effects and also the toxicity of a chemical entity, these factors are responsible for the success or failure of a drug candidate.
Prepare isolable quantities of drug metabolites in non-aqueous conditions; synthesize on Correlate isolated metabolites with those obtained from clinically isolated phenotypes Design an efficient method for the systematic preparation and identification of the entire
spectrum of metabolites from a chosen drug multi-gram scale
Detect any pharmaceutical products and their metabolites from serum, blood and urine using a
chromatographic procedure with fluorescence detection or with added chromophores
This approach affords an efficient method for the systematic preparation and identification of the entire spectrum of metabolites from a chosen drug. We have developed rare examples of catalyst mediated oxidation of sophisticated pharmaceutical entities. Our reactions are generally applicable and have been used in our laboratories to achieve hydroxylation and N-demethylation on numerous other substrates. The hydroxy metabolite and the desmethyl derivative were usually difficult to synthesize by conventional organic chemistry methods. With Biomimiks we can screen a series of compounds by reacting them with different permutations of azamacrocycle, co-oxidant and a suitable solvent. This logically leads to subsequent scaled-up optimal processes. The oxidation products can then be separated and subjected to toxicologic, pathologic, histopathalogic, or genotoxic testing.
Screen a broad range of chemical entities with a compendium of our proprietary oxidation catalyst and
co-oxidants, generating a complete range of metabolites.
Prepare metabolites on multi-gram scale. Our sterically protected and electronically activated catalysts
provide high catalytic turnover and reaction rate.
- The scaled up products can then be separated and made available for toxicologic, pathologic, histopathalogic, or genotoxic testing.
Assay metabolites for clinical testing and profiling with our proprietary azamacrocycles
(synthetic livers). We would conduct the following analysis:
- Screen by reacting medications for a specific indication and any other medications the patient is taking with different permutations of a catalyst, co-oxidant and a suitable solvent. - Define reaction and HPLC/Mass Spec analysis conditions that produce the maximum number of metabolites. - Analyze the phenotypes, blood, urine and saliva of target patients by HPLC and determine the metabolic profile of specific drugs. Compare the proportion of metabolites with those experimentally observed in vitro. - Analyze metabolites of other medications prescribed for patients. Look for evidence of suppression or attenuation of metabolites to determine drug-drug interactions.
Empirikos Biomimiks technology is an excellent addition to rational drug development and lays the predictive foundation for emulating biological structure, function, mechanism and reactivity. In addition, before administration of a new drug to a patient, Biomimiks technology allows physicians to predict the effectiveness of the new drug within the context of a patients existing therapies.
About Empiriko
Empiriko is a Clinical Intelligence Technology (CIT) company that is taking a unique, holistic approach to drug discovery, development and patient outcomes by integrating and leveraging knowledge from scientific research, clinical experiences, observations and available patient data using sophisticated algorithms, advanced analytics, predictive modeling and scientific and clinical interpretation of research data. To achieve a higher level of predictive power, Empiriko is designing biomimetic systems that emulate biological structure, function, mechanism and reactivity. Unlike traditional in silico or computerized models, Empiriko works collaboratively with academic institutes and drug discovery companies to iteratively test and refine computerized models in a laboratory environment. Our proprietary Biomimiks solutions generate metabolite data that contributes to making Empiriko models (disease, patient and drug) more robust and improving the predictive power of the CIT platform. These models are used to connect drug discovery to patient outcomes, so the right therapies are developed for the right subpopulation, and physicians are able to treat patients more effectively.