Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain
These studies represent the first demonstration of a reduction of brain Aβin vivo and will enable a clinical examination of the Aβ hypothesis that Aβ peptide drives the neuropathology observed in Alzheimer's disease.
In Vivo Assessment of Brain Interstitial Fluid with Microdialysis Reveals Plaque-Associated Changes in Amyloid-β Metabolism and Half-Life
By rapidly inhibiting Aβ production, it is found that ISF Aβ half-life was short in young mice but was twofold longer in mice with Aβ deposits, which suggests that inhibition of Aβ synthesis reveals a portion of the insoluble Aβ pool that is in dynamic equilibrium with ISf Aβ.
Robust Central Reduction of Amyloid-β in Humans with an Orally Available, Non-Peptidic β-Secretase Inhibitor
The magnitude and duration of central Aβ reduction obtainable with BACE1 inhibition positions this protease as a tractable small-molecule target through which to test the amyloid hypothesis in man.
Histone Modifications and Cancer.
Many of the key and newly identified histone modifications known to be deregulated in cancer and how this impacts function are reviewed.
The promise and peril of chemical probes.
A community-driven wiki resource to improve quality and convey current best practice on chemical probes, and to help address shortcomings of poor quality or that are used incorrectly generate misleading results.
The Potent BACE1 Inhibitor LY2886721 Elicits Robust Central Aβ Pharmacodynamic Responses in Mice, Dogs, and Humans
Nonclinical and early clinical development of LY2886721 is reported, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD and has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models.
EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation.
Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor.
The affinity of a compound for the 5-HT2F receptor at 37 degrees versus 0 degree was shown to be useful for predicting agonist or antagonist activity, and information is provided about some of the structural requirements for the affinity of certain tryptamines at the 4-HT/1C receptor family.
5‐HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs
The potency of agonists in inhibiting adenylate cyclase in cells transfected with human 5-HT1F receptor was also highly correlated with their potency in the animal model of migraine, suggesting that the 5- HT1F receptors is a rational target for migraine therapeutics.
Potent, selective tetrahydro-beta-carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus.
As the first compounds reported with such selectivity and enhanced receptor affinity, these tetrahydro-beta-carboline antagonists are useful tools for elucidating the role of serotonin acting at the 5HT2B receptor in normal and disease physiology.