Structure-Based Development of Novel Spiro-Piperidine ASH1L Inhibitors.

The absent, small, or homeotic-like 1 (ASH1L) protein is a histone lysine methyltransferase that plays a crucial role in various cancers, including leukemia. Despite representing an attractive therapeutic target, only one class of ASH1L inhibitors was identified to date. Herein, we report development of advanced ASH1L inhibitors targeting the catalytic SET domain, which were designed to access previously unexplored binding pocket on ASH1L.

Jet-Cooled Phosphorescence Excitation Spectrum of the T(n,π*) ← S Transition of 4-Pyran-4-one.

The 4-pyran-4-one (4PN) molecule is a cyclic conjugated enone with spectroscopically accessible singlet and triplet (n,π*)excited states. Vibronic spectra of 4PN provide a stringent test of electronic-structure calculations, through comparison of predicted vs measured vibrational frequencies in the excited state. We report here the T(n,π*) ← S phosphorescence excitation spectrum of 4PN, recorded under the cooling conditions of a supersonic free-jet expansion.