Tag Archives: CNS penetration

Review: Optimizing CNS access


Neurotherapeutic agents generally illicit their effects by acting on receptors in the central nervous system (CNS) and a short review in Expert Opin. Drug Discov. highlights the current best practices and recent developments in targeting molecules to the brain.  The … Continue reading

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Optimization of plasma protein binding (again…)


Following hot on the heels of the Pfizer paper we blogged recently, comes a very similar publication from scientists at Genentech/Depomed.  Titled ‘Do We Need to Optimize Plasma Protein and Tissue Binding in Drug Discovery?’, the authors highlight the apparent … Continue reading

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Structure-based design of BACE inhibitors


In a recent post the difficulties of developing drug-like and CNS penetrant inhibitors of β-secretase (BACE-1 or ASP-2) were hinted at (a detailed account of the state of the art can be found in this book).  Many of the reported inhibitors … Continue reading

Posted in Computational Methods, Enzyme Inhibitors, Med Chem Strategy | Tagged , , , , , , , , , , , , , , | 1 Comment

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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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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