6) Complete mechanism of metabolic clearance experiments #124

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alintheopen opened this Issue Jan 8, 2014 · 3 comments

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alintheopen commented Jan 8, 2014

Further information required on metabolic clearance for series four compounds.
@mattodd - do we need to send more compounds?

@ghost ghost assigned mattodd Jan 8, 2014

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mattodd commented Jan 18, 2014

Context: Compounds under discussion, with data: http://malaria.ourexperiment.org/biological_data/8464
i.e. MMV669844, MMV669848, MMV670936

Meeting minutes: http://malaria.ourexperiment.org/osddmalaria_meeting_/8407 containing the rationale, which is that ID of the mechanism of metabolic clearance may suggest ways of reducing this and improving PK properties.

Implication in the discussion was that the Charman lab already had enough of these compounds, or that there were samples remaining. Spreadsheet of remaining amounts: http://malaria.ourexperiment.org/osdd_malaria_shared/8106
...which suggests:

MMV669844 has 137 mg left,
MMV669848 has 46 mg left
MMV670936 has 270 mg left

Not clear if this is before or after the samples were sent to Charman. I will check with Paul Willis whether this will be enough compound for the required metID experiments, on the fair assumption that the same compounds would be used. If there is enough available material, then no further action is needed until those data are obtained and this issue could then be closed.

@ghost ghost assigned PaulWillisMMV Jan 19, 2014

It would also be interesting to oxidize the triazolopyrazine core of one of the MMV compounds, figure out which nitrogen has become the N-oxide (C-NMR & N-NMR). If it matches one of the metabolites detected at Monash University, it should be tested in the relevant assay to find out if this metabolic pathway is detrimental for the biological activity.

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mattodd commented Mar 26, 2014

Updated amounts from Paul Willis March 2014:
MMV669844 has 42 mg left,
MMV669848 has 27 mg left
MMV670936 has 266 mg left
in case these are needed for further study.

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