ENU-based dominant genetic screen identifies contractile and neuronal gene mutations in congenital heart disease.

Background: Congenital heart disease (CHD) is the most prevalent congenital anomaly, but its underlying causes are still not fully understood. It is believed that multiple rare genetic mutations may contribute to the development of CHD.

Methods: In this study, we aimed to identify novel genetic risk factors for CHD using an ENU-based dominant genetic screen in mice.

Ritonavir Revisited: Melt Crystallization Can Easily Find the Late-Appearing Polymorph II and Unexpectedly Discover a New Polymorph III.

Identification of a thermodynamically stable polymorph is an important step in the early stage of drug development. Ritonavir (RIT) is a well-known case where the most stable polymorph II emerged after being marketed, leading to a loss of $250 million. Herein, we report the findings that routine melt crystallization can reveal the late-appearing polymorph II of RIT at small supercooling, but the probability of nucleation is very low.

Rich polymorphism in nicotinamide revealed by melt crystallization and crystal structure prediction.

Overprediction is a major limitation of current crystal structure prediction (CSP) methods. It is difficult to determine whether computer-predicted polymorphic structures are artefacts of the calculation model or are polymorphs that have not yet been found. Here, we reported the well-known vitamin nicotinamide (NIC) to be a highly polymorphic compound with nine solved single-crystal structures determined by performing melt crystallization.

A general method for cultivating single crystals from melt microdroplets.

The cultivation of single crystals from solution is usually a time-consuming trial-and-error process. Here, we report a general strategy for rapidly cultivating single crystals from melt microdroplets within tens of minutes at the microgram scale. This strategy was successfully applied to the important polymorphic system griseofulvin to provide missing structural information of Form III, for which single crystals could not be cultivated from solution, as well as to twenty clinical drugs to verify its generality.