Natural Science > Chemistry > DG CY2020 8027

Research Title Cell-based ADMET Assays (Year 2 of 1)
Research Personnel Leader:
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Research Duration Start:
End:
3 January 2019
30 November 2019
Research Location UPD-NIMBB
Research Description The program will establish the requisite in vitro and in vivo (animal) ADME-Tox assays to help identify the best iteration of the lead compounds in the drug discovery pipeline. The suite of assays can constitute the bulk of ADME-Tox package that will be required by regulatory authorities for an investigational new drug application (IND). Most of the assays to be described are in vitro, for several reasons. Firstly, they are simple, convenient, and provide a fast way of testing the drug-like properties of a lead series. Secondly, they require limited amounts of a test compound. Thirdly, SAR studies for metabolic activity are in fact more difficult to study animals because of confounding factors. Lastly, speciesrelated differences make ADME studies in animals less appealing, as they often fail to estimate human clinical outcomes.
Research Objectives 1. To determine the permeability of candidate compounds in model cell lines expressing relevant influx and efflux transporters (MDCK and Caco-2 cells); 2. To identify/phenotype which of the following CYP450 enzymes may be responsible for metabolizing the candidate compounds: CYP3A4, CYP2D6, CYP2C8/9, CYP1A2, CYP2C19; 3. To determine the ability of candidate compounds to induce or inhibit the aboye CYP450 isozymes; 4. To determine the toxic liabilities of candidate compounds in liver, kidney, heart, vascular endothelial, neuronal and skeletal muscle.
Research Beneficiary(ies) The study will provide lead optimized compounds(i.e., compounds with most drug-like features) for downstream formulation, pre clinical and clinical studies. These high value compounds can be licensed out or partnered for further development. This will benefit all parties involved in their discovery and development as joint owners of all intellectual property generated. Most importantly, patients are the ultimate beneficiaries should the drugs survive clinical trials and FDA approval
Research Accoplishments [CY 2018] 1) Compound iterations with desirable permeability characteristics; 2) Compounds with no to minimal safety issues in terms of inducing or inhibiting CYP450 drug metabolizing enzymes; 3) Compounds with no to minimal toxicity to major issues of the body
Total Research Cost ₱28,934,665.44
Research Agencies Funding:
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UPD-NIMBB


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Code DG CY2020 8027
KRA Code
Priority Thrust DOST
R&D


Sector Natural Sciences
Actual Sector Chemistry
Related sectors Medical science
Entry revision: February 2021