Drug Discovery
Shared Resource Director: Sulma
Mohammed
E-mail: mohammes@purdue.edu
Department: Veterinary Clinical Sciences
Phone: (765) 494-9948
Buildings/Rooms: VPRB 12; LYNN 1339
General Information and Services
The Drug Discovery Shared Resource provides essential
services for Purdue Cancer Center investigators whose research focuses
on the design, synthesis and evaluation of novel anticancer agents
and diagnostics. It provides a highly integrated service for the evaluation
of candidate compounds in vitro and in vivo.
The Drug Discovery Shared Resource provides investigators with in
vitro assays assessing inhibition of cell proliferation and will provide
more specific screens targeting cell signaling cascades, cell cycle
regulation, and induction of apoptosis.
Xenograft assays in athymic mice are available to provide in vivo
assessment of antitumor activity. Human tumor cell lines of many histologic
types are available for use; mechanistic information will be used
to select cell lines for specifically targeted drug candidates. The
majority of these cell lines also are available as xenografts so that
promising candidates in vitro can be carried forward directly into
in vivo models.
Most drug evaluations in vivo will rely on standard subcutaneous xenograft
models; facility staff will work with investigators to select appropriate
in vitro and in vivo models, drug vehicle, and administration schedule.
Expertise in experimental pathology is provided to assist in study
design and evaluation of tumor response.
Ultimately, the goal of the Drug Discovery Shared Resource is to provide
the essential expertise, services and data needed to move promising
drug candidates toward further pre-clinical development in preparation
for clinical evaluation.
Services Provided
The Drug Discovery Shared Resource provides a wide variety of services
to evaluate the potential value of new drug and diagnostic candidates.
In Vitro in Cell Culture
Defined protocols are available for PC3 (prostate), MDA231 and MCF-7
(breast), HT29 (colon), HT1376, UMUC3 (bladder), PACA2 (pancreas),
KB (nasopharyngeal), A549 (lung), and other cells. Typically a drug
with five concentrations per cell line is used. The IC50 for a drug
is determined.
In Vivo Animal Models
Compounds showing significant target or growth inhibition in vitro
cell culture systems can be tested in additional cell lines or submitted
to the NCI for evaluation in their panel.
Specialized panels have been developed to meet the needs of specific
investigators. Xenograft studies in athymic mice are carried out using
a number of different cell lines, including A549 (lung), A498-2/LM
(renal), HT-29 (colon), KB (nasopharyngeal), PACA2 (pancreas) and
UMUC3 and HT1376 (urinary bladder).
The Shared Resource staff administer the test compounds, monitor mouse
body weight and tumor size, watch for overt signs of toxicity, and
perform euthanasia.
A Veterinary pathologist provides post-mortem evaluation, routine
tissue processing and evaluation.
Before compounds enter xenograph testing, initial studies assessing
the gross toxicity are performed to define a maximum tolerated dose
for therapeutic evaluation. Consultation is provided by the Director
regarding suitability of particular models and experimental design.
Drug Discovery Rates
(Rates for Cancer Center members will be discounted)
In Vivo subcutaneous: $1,700
Orthotopics Injection: $2,200.00
Tumor Cell Implantation: $400.00
Toxicity: $130.00
In Vitro (per cell line): $70.00
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