Category Archives: Clinical Candidates

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

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Discovery of MK-1220 (Hepatitis C NS3/4A protease inhibitor)


A recent letter in ACS Med.Chem.Lett. details the optimisation of a series of inhibitors of the Hepatitis C virus (HCV) NS3/4A protease, and is interesting in that it provides detailed pharmacokinetic data for a series of macrocyclic lactones, a class of therapeutic … Continue reading

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TAK-733 & CH4987655 (Allosteric MEK Inhibitors)


The mitogen-activated protein kinase (MAPK) signalling cascade is one of the key pathways regulating cell proliferation and differentiation and aberrant activation of this pathway is implicated in a number of cancers. Targeting components of the cascade thus has the potential … Continue reading

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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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Discovery of LX2931 (Sphingosine 1-Phosphate Lyase Inhibitor) & Phase IIa Data


Fingolimod (FTY720, Gilenya), an immunosuppresive agent with activity purported to be mediated by binding of it’s phosphorylated derivative to the sphingosine-1-phosphate receptor 1 (S1P1), was approved earlier in the year as the first orally administered disease modifying therapy for the treatment … 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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The Discovery of RG1678 (Gly-T1 inhibitor)


In this interesting J.Med.Chem. article workers from Roche describe the optimisation of a series of benzoylpiperazines as Gly-T1 inhibitors for the treatment of schizophrenia culminating in the discovery of RG1678, the first potent and selective Gly-T1 inhibitor to demonstrate efficacy … Continue reading

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