Design and synthesis of novel fluorescently labeled analogs of vemurafenib targeting MKK4

The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in liver regeneration and is under investigation as a target for stimulating hepatocytes to increased proliferation. Therefore, new small molecules inhibiting MKK4 may represent a promising approach for treating acute and chronic liver diseases. Fluorescently labeled compounds are useful tools for high-throughput screenings of large compound libraries. Here we utilized the azaindole-based scaffold of FDA-approved BRAF inhibitor vemurafenib 1, which displays off-target activity on MKK4, as a starting point in our fluorescent compound design. Chemical variation of the scaffold and optimization led to a selection of fluorescent 5-TAMRA derivatives which possess high binding affinities on MKK4. Compound 45 represents a suitable tool compound for Fluorescence polarization assays to identify new small-molecule inhibitors of MKK4

Cross-lagged analysis of reciprocal effects of morphological awareness and reading in Chinese in a multilingual context

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Background: While much is known about how morphological awareness (MA) contributes to reading development, little attention has been paid to how reading may conversely affect MA development, particularly in readers of Chinese in a bilingual/multilingual setting. Methods: The study adopted a cross-lagged panel design. Young bilingual readers of Chinese were measured in MA, word reading, and reading comprehension – all in Chinese – twice from Grade 3 to Grade 4. Results: Path analysis revealed that Grade 3 MA significantly predicted Grade 4 reading comprehension after controlling for the autoregressive effect. Over and above Grade 3 MA, Grade 3 reading also significantly predicted Grade 4 MA. Subsequent analyses, however, revealed disparate developmental patterns between those with Chinese and English, respectively, as their home language. Implications: These findings, while supporting reciprocity of developmental relationships between MA and reading, also suggested that the pattern of relationships can vary as a function of students’ target language experiences in a bilingual/multilingual setting.The study reported in this paper was part of a large project that examined Singaporean children’s biliteracy development. The project was supported by a grant from the Office of Education Research of National Institute of Education, Nanyang Technological University (grant number: OER 24/10 ZDB). No views expressed in this paper represent those of the funding agency or any author’s affiliated organization