Testing of Compounds in Rat Pharmacokinetic Studies

The National Center for Advancing Translational Sciences (NCATS) is a translational science center that prides itself on its productive pipeline and is innovative in a number of ways. NCATS brings together a diverse range of scientists, including medicinal chemists, biologists, toxicologists, and engineers, in order to ultimately translate basic science into real products and services that help improve people’s lives. Included in this process is the development of unique small molecules as potential anticancer agents.

Prior work at NCATS has produced a series of small molecule inhibitors, including NCGC00371481 and its structural analogs.  Compounds such as ‘1481 have shown promising results in cellular and mouse models of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).  Further optimization of the biochemical, physiochemical and pharmacokinetic properties of these compounds is required, and may eventually produce a clinical candidate that could be used to treat cancers such as MDS and / or AML. 

In order for a candidate compound to advance into clinical trials, it must display a wide range of acceptable properties.  For this program, a potential clinical candidate must display potent inhibition of the desired targets.  It must also display suitable pharmacokinetic (PK) properties in a range of preclinical species, including at least one rodent species (mouse or rat), as well as at least one higher preclinical species (dog or monkey).  Good PK profiles in these species are required in order to 1) build models that predict good pharmacokinetic properties in humans and 2) so that compounds can be given at high doses and high plasma exposure levels in preclinical safety studies.

In order to characterize and optimize the pharmacokinetic properties of compounds in rats, NCATS is seeking to run a series of rat pharmacokinetic experiments.  Testing a set of 20 small molecule compounds in rat PK studies will provide critical data that identify the strengths and weaknesses of current compounds’ PK profiles, and will help optimize those profiles so that NCATS can identify a suitable candidate for clinical trials.

Purpose and Objectives: The purpose of this acquisition is to acquire testing services of 20 small molecule compounds in rat pharmacokinetic studies.

Please refer to the Statement of Work (Attachment 1) for additional information.