Tag Archives: Pfizer

Drug discovery approaches to minimise drug induced liver injury in man


The recent literature has seen a flurry of papers describing the issue of, and potential approaches to minimising the incidence of, drug-induced liver injury (DILI) in the clinic.   It is well recognised that attrition throughout the development pipeline is often … Continue reading

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Discovery of PF-04691502 (PI3K/mTOR dual inhibitor)


Rapamycin and it’s analogues (or rapalogues e.g. CCI-779) modulate the phosphatidylinositol 3-kinase (PI3K) signalling cascade by binding to an allosteric site on the mTORC1 complex (Mammalian target of rapamycin (mTOR), a class IV PI3K protein kinase, forms two functional complexes, … Continue reading

Posted in Clinical Candidates, Enzyme Inhibitors, Kinase Inhibitors, Kinases, Med Chem Strategy | Tagged , , , , , , , , , , , , , , , , , , , , , , , | Leave a comment

Discovery of PF-232798 (CCR5 Antagonist)


CCR5 antagonists prevent entry of HIV into host cells by binding to the CCR5 co-receptor and stopping the gp120-CD4 complex from making the crucial interaction with CCR5 that leads to fusion of the viral and host cell membranes (see Wikipedia article … Continue reading

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PoseView


Workers at the Center for Bioinformatics, University of Hamburg recently published an article describing a freely accessible web-based application (PoseView) which automatically generates two-dimensional diagrams of macromolecular complexes illustrating the key ligand-protein interactions.   In the article the authors describe the … Continue reading

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Efficacy and plasma protein binding


The December issue of Nature Reviews|Drug Discovery includes an informative article from scientists at Pfizer titled ‘The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery’.  In it they discuss the ways in which plasma protein … Continue reading

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Aromatic chloride to nitrile transformation


Introducing a nitrile in the place of less polar substituents is a fairly common approach to reducing lipophilicity in a lead molecule but in this review from the MedChem group at Pfizer the associated benefits of specifically the aromatic chloride to … Continue reading

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Discovery of PF-04457845 (FAAH Inhibitor)


In this latest publication from the Pfizer labs, the authors describe their continuing efforts to identify urea-based, irreversible inhibitors of fatty acid amide hydrolase (FAAH).  Inhibition of FAAH and the concomitant elevation of endogenous levels of fatty acid amides has … Continue reading

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