Structural and biochemical insights into purine-based drug molecules in hBRD2 delineate a unique binding mode opening new vistas in the design of inhibitors of the BET family.

The bromodomain and extra-terminal (BET) family proteins, which are involved in chromatin function, have been shown to be promising drug targets in several pathological conditions, including cancer and inflammation. There is considerable interest in the development of BET inhibitors with novel scaffolds to modulate the epigenesis of such diseases. Here, high-resolution crystal structures of the purine class of FDA-approved drugs (theophylline, doxophylline and acyclovir) and non-FDA-approved compounds (3-methyl-7-propylxanthine and theobromine) complexed with hBRD2 bromodomains BD1 and BD2 are reported.

Cloning, Expression and Characterization of Spore Wall Protein 5 (SWP5) of Indian Isolate NIK-1S of Nosema bombycis.

SWPs are the major virulence component of microsporidian spores. In microsporidia, SWPs can be found either in exospore or endospore to serve as a putative virulence factor for host cell invasion. SWP5 is a vital protein that involves in exospore localization and supports the structural integrity of the spore wall and this action potentially modulates the course of infection in N.

Profilin is involved in G1 to S phase progression and mitotic spindle orientation during Leishmania donovani cell division cycle.

Profilin is a multi-ligand binding protein, which is a key regulator of actin dynamics and involved in regulating several cellular functions. It is present in all eukaryotes, including trypanosomatids such as Leishmania. However, not much is known about its functions in these organisms.

Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action.

Mutations in MEK1/2 have been described as a resistance mechanism to BRAF/MEK inhibitor treatment. We report the discovery of a novel ATP-competitive MEK1/2 inhibitor with efficacy in wildtype (WT) and mutant MEK12 models. Starting from a HTS hit, we obtained selective, cellularly active compounds that showed equipotent inhibition of WT MEK1/2 and a panel of MEK1/2 mutant cell lines.