We want to make a difference in how drugs are discovered. Generally, our collaborators have developed interesting biology and have access to assays and animal models to confirm the activity of molecules. We use AVO (Autonomous Virtual Organism) to accelerate the discovery of viable lead compounds and preclinical candidates.
Select a stage below to explore how Evince works with partners:
Define the project
- Primary targets of interest
- ADME filters
- Evince screening library
- Evince repurposable library
- Partner library*
* Can be integrated in a blinded fashion via the cloud so Evince does not see the molecules
Program the targets and library(ies)
- Evince trains the primary target of interest, counter-screen(s) and ADME predictors
- Targets and ADME predictiors that are already in AVO do not need to be retrained
- Existing library(ies) can be immediately used
- Any new libraries are processed locally or in the cloud
Screen library(ies) and select the best drug-like leads
Find drug-like lead(s)
- The resulting molecules are not merely "hits"
- "Drug-like leads" also include analysis of counter-screen(s) and ADME properties
Each molecule is scored in each screen and selected ADME property
Molecules can be evaluated based on individual scores or on composite scores of several or all screens and ADME filters
The "best" molecules are selected for lead optimization based on individual or composite scores
AVO Lead Optimization
- 9-12 months; 5-10 medicinal chemistry cycles
- Includes synthesizing molecules and laboratory assays
- Indicates which chemical changes had a favorable impact
- Provides strategy for next cycle of medicinal chemistry to fine-tune the analog library
- Test the molecules to confirm predicted characteristics
- May run multiple in silico cycles before lab testing
Select a Preclinical Candidate
- Medicinal chemistry is applied until a viable preclinical candidate and back-up molecules are identified
- Selection is made based on traditional laboratory assays and animal testing
- Hit. A hit is a compound that has the desired activity in a compound screen and whose activity is confirmed upon retesting.
- Hit to Lead. The aim of this stage of the work is to refine each hit series to produce more potent and selective compounds which possess pharmacokinetic properties appropriate for further characterization in vivo. Typically, the work now consists of intensive structure activity relationship (SAR) investigations around each core compound structure, with measurements being made to establish the relative activities of each analog.
- Lead Compound. Structure that has activity against the chosen target, as well as appropriate ADME characteristics, but not yet good enough to be the drug itself.
- ADME. The four processes involved when a drug is taken are absorption, distribution, metabolism and elimination or excretion (ADME). Pharmacokinetics is the way the body acts on the drug once it is administered. It is the measure of the rate (kinetics) of absorption, distribution, metabolism and excretion (ADME). All the four processes involve drug movement across the membranes.
- Lead Optimization. The object of this final drug discovery phase, which is the most intensive and costly phase, is to maintain favorable properties in lead compounds while improving on deficiencies in the lead structure. Compounds at this stage may be deemed to have met the initial goals of the lead optimization phase and are ready for final characterization before being declared as a preclinical candidate.
- Preclinical Candidate. A member of a biologically and pharmacologically active compound series with desired potency, selectivity, pharmacokinetic, pharmacodynamic and toxicity properties that can advance to IND-enabling studies (studies required by regulatory agencies like the FDA prior to testing in humans) for clinical candidate selection.