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Histone Deacetylase (HDAC) Inhibitor Kinetic Rate Constants Correlate with Cellular Histone Acetylation but Not Transcription and Cell Viability
Evaluating HDAC inhibitor properties using histone acetylation is not predictive of their function on cellular activity, and a panel of benzamide-containingHDACi are slow tight-binding inhibitors with long residence times unlike the hydroxamate-containing HDACi vorinostat and trichostatin-A.
GDC-0449-a potent inhibitor of the hedgehog pathway.
Liposomal Packaging Generates Wnt Protein with In Vivo Biological Activity
When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.
Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer.
The discovery of 2 (GDC-0980), a class I PI3K and mTOR kinase inhibitor for oncology indications, has demonstrated significant efficacy in mouse xenografts when dosed as low as 1 mg/kg orally and is currently in phase I clinical trials for cancer.
Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor.
Total synthesis of brevetoxin A
The convergent synthesis reported here renders this scarce neurotoxin synthetically available and, more importantly, allows the design and synthesis of analogues for further biochemical studies.
Rational design of phosphoinositide 3-kinase α inhibitors that exhibit selectivity over the phosphoinositide 3-kinase β isoform.
It is proposed that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 ofPI3Kα that is not attained with the corresponding Lys777 of PI3Kβ that can be rationalized by the difference in electrostatic potential between the two isoforms in a given region.
Second generation 2-pyridyl biphenyl amide inhibitors of the hedgehog pathway.
Callipeltoside a: total synthesis, assignment of the absolute and relative configuration, and evaluation of synthetic analogues.
The total synthesis of the novel antitumor agent callipeltoside A, as well as several analogues, is accomplished and allows assignment of the stereochemistry not previously established and the excellent chemo- and regioselectivity highlights the synthetic potential of this new ruthenium catalyzed process.
The Wittig and Related Reactions in Natural Product Synthesis
Originally reported in Liebigs Annalen in 1953 (then called Justus Liebigs Annalen der Chemie), the Wittig reaction has evolved to include the Horner–Wittig and Horner–Wadsworth–Emmons reactions and