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Lead Discovery |  |
Lead Optimization |  |
Preclinical Development |  |
Clinical Development |  |
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Lead Optimization Rich SAR information from Pharmacopeia’s unique lead discovery platform contributes to accelerated optimization. Pharmacopeia is able to plot the frequency with which certain subsituents or chemical groups contribute to biological activity for compounds based on the same, or even different, scaffolds. This information is invaluable to the medicinal chemist to guide productive and rapid optimization. |
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Understanding ADME and Toxicity Characteristics of New Molecules To complement Library Profiler, we developed a program called ADME Profiler for analysis of discrete compounds rather than libraries. Along with public models, ADME Profiler has a proprietary model of hERG inhibition. The interactive graphing combined with computational models encourages scientists to further explore computational and experimental data and thereby develop informed hypotheses on how to solve ADME/Tox issues. The early identification and elimination of compounds with toxicity issues saves considerable time, effort and cost being applied to compound series that will likely fail during pre-clinical profiling. We believe our success at this has contributed to Pharmacopeia’s impressive track-record and very low rates of compound failure in pre-clinical development. |
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Pharmacopeia pursues multi-parameter lead optimization to advance lead compounds emerging from Hit to Lead efforts rapidly to clinical candidates. The iterative process, illustrated in the figure opposite, will seek to optimize chemical structure against a wide-range of parameters simultaneously. Such parameters include, but are not limited to:
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In vivo Optimization The in vivo activity of our lead compounds are assessed through a combination of internal platforms and collaborations with CROs and academia. The ability to assess a compound’s exposure, at an early stage of our project, through measurement of blood levels following intravenous (i.v.), intraperitoneal (i.p.) or oral (p.o.) administration is an important assessment to not only determine a compound’s bioavailability, but also to select the most appropriate lead series from our lead discovery programs which, typically, offer Pharmacopeia scientists multiple distinct chemical starting points. For our internal research projects, we assess drug action through mechanistic or proof-of-principle studies. For example, we measure the amount of protein produced in plasma in response to cytokine administration. We collaborate with both CROs and academia to obtain efficacy data in disease models, particularly in the areas of inflammation and immunobiology. In our collaborative drug-discovery programs our partners will typically, though not always, be responsible for determining the in vivo efficacy of compounds in relevant animal models. |
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Early ADME/Tox Determination Pharmacopeia’s approach to the early determination of ADME/Tox liabilities is one of the key enablers of Pharmacopeia’s ability to rapidly and successfully advance compounds into clinical development. Available as rapid in vitro screens, we have established assays to assess absorption, solubility, metabolic susceptibility, and some key toxicity indicators such as hERG channel inhibition. Additional information, such as CYP induction, and metabolite ID, are obtained through collaborations with CRO’s. |
