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Advanced Drug Discovery & Development Services

Target-based vs. Phenotype-based

Drug Discovery

The drug discovery process for researching and developing new medicines is growing in difficulty and length. On average, it takes at least ten years and with an estimated average cost of billions of dollars to bring a new medicine to market [1,2]. The human and financial cost of failures is enormous due to the fact that thousands and sometimes millions of compounds may be screened and assessed early in the R&D process, but only a few will ultimately receive approval. For early-stage biotech and pharma companies, the return is even lower because they don’t have many compounds to screen.

A recent study of approved drugs revealed that Target-based Drug Discovery, or TDD, is underperforming relative to Phenotype-based Drug Discovery, or PDD. PDD focuses on ameliorating phenotypes to discover efficacious drugs, whereas TDD focuses on interactions with pre-identified drug targets. Looking broadly back over the past two decades, the PDD approach has resulted in twice as many approved new drugs as TDD[3]. Small and large pharma companies can benefit from broadening their PDD programs. By focusing on the phenotype, efficacious drugs are identified more quickly and readily, costing less time and money.

 Target-based Drug Discovery

Phenotype-based Drug Discovery

Requires an identified target

No target identification needed

Unsophisticated cell lines /methods can be used

More complex genetic models are needed

Output is molecular and requires later efficacy testing

Output is functional, and may need later MMOA identification

Our Offerings

Two of our most common services are:

Compound Efficacy Assessment | InVivo Biosystems

Compound Efficacy Assessment

Testing new compounds and formulations to understand whether they are functionally effective on disease phenotypes.

Mechanism of Action Studies | InVivo Biosystems

Mechanism of Action Studies

Creating “Clinical Avatars” by inserting the disease gene variant into a model to create humanized animal model(s) that express human disease genes.

Other Services and Testing

We also perform other specialized testing and analysis including:

Data example: By combining a highly sensitive larval growth assay with a highly selective egg viability assay, we can refine the pool of possible compounds or dosages to those least (or most) likely to be toxic.

Two complementary approaches to testing developmental toxicity in C. elegans
A) Larval growth assay violin plot shows distribution of worm length measured by high resolution imaging and automated worm detection. Darker blue indicates higher drug concentration. Day 1 = L2/L3, day 2 = L4, day 3 = adult.
B) Egg viability assay showing the average proportion outcomes for 50 embryos 3 days after laying. EC = effective concentration relative to maximal response of a fluorescent stress reporter. Learn more about our In Vivo Toxicity Testing.

Mapping of gene expression data to longevity pathways in the KEGG database
Pathway shown represents changes of expression that might be observed under conditions of dietary restriction. Pathway components are color coded based on the level of up or down regulation of treated samples versus control.

Learn more about our Lifespan and Healthspan Analysis.

References

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