Horizon eBook - 7

Innovations in Cell-Based Screening * Phenotypic Screens Rise in Popularity

In the laboratory, the imaging is compatible with
different tissue formats, including tumor spheroids
grown in bioreactors or in multiwell plates, as well as
tissue biopsies and other organotypic models. It can be
used in assays for chemosensitivity and resistance and
toxicity screening.
This year, Anidyn will introduce new
components and software that will help users
integrate its platform with Zeiss and Nikon inverted
microscopes. The idea is to allow standard issue
microscopes to show changes in a cell's phenotype
in real time.
Affinity Chromatography
Analytical methods such as chromatography
are also coming into play. Shantani, a chemical
proteomics company based in Mumbai, has
developed an affinity chromatography method
designed to identify targets from phenotypic screening
and to help clarify the mechanism of action.
According to CEO Chaitanya Saxena, Ph.D.,
Shantani's products are a subcellular location
specific (SCLS) target-capture technology and a
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unique polymer technology (UPT). These technologies,
which identify targets from phenotypic screening
hits, differ significantly from current target identification approaches that require substantial amounts
of structure-activity-relation (SAR) information on
hit molecules, notes Dr. Saxena, who adds that with
UPT, hits can be used directly for target identification.
According to Dr. Saxena, Shantani's approaches
to identify targets and trace mechanisms of action are
significantly faster, simpler, and more cost-effective
than alternatives. He claims that the company's UPT,
for instance, can generate target identification information in as little as three weeks.
Shantani is using these methods in its own drug
development efforts, which already have identified a
new target for a metabolic disorder. The firm expects
to shortly start IND-enabling studies on optimized
lead molecules for a type-2 diabetes target. The company is also collaborating with a top 10 pharmaceutical company on an oncology drug-a non-kinase,
non-VEGF, non-vascular disrupting agent for antiangiogenesis therapy, points out Dr. Saxena.
He admits that the company's SCLS methods

are limited to cellular models. They have not been
used in animal screens, and they have not been
tested in screens that involve neuronal cultures.
Targeting Alzheimer's Disease
Phenotypic drug development is also proving
important for an area where many drug discovery
and development projects have failed: Alzheimer's
therapies. Ultimately, the field must be driven to
target-based screening, says Tae-Wan Kim, Ph.D.,
associate professor of pathology and cell biology at
Columbia University Medical Center. But, to date,
not much high-throughput screening has been done.
"The data is there for cancer, but with Alzheimer's,
we're not there yet," cautions Dr. Kim, citing a clinical
trial success rate for Alzheimer's drugs of 0.4%.
Phenotypic methods will be necessary to
better understand Alzheimer's and other complex
disorders, he continues, adding that his teams are
using phenotypic, high-throughput screening
platforms targeting cellular pathways to Alzheimer's,
including beta secretase (BACE 1) inhibitors, Tau
protein modulators, and apolipoprotein E (ApoE)



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Horizon eBook

Table of Contents for the Digital Edition of Horizon eBook

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