Control of a Production Manipulator with the Use of BCI in Conjunction with an Industrial PLC.

Research in the field of gathering and analyzing biological signals is growing. The sensors are becoming more available and more non-invasive for examining such signals, which in the past required the inconvenient acquisition of data. This was achieved mainly by the fact that biological sensors were able to be built into wearable and portable devices.

Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity.

ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While ASH1L represents an attractive drug target, developing ASH1L inhibitors is challenging, as the catalytic SET domain adapts an inactive conformation with autoinhibitory loop blocking the access to the active site. Here, by applying fragment-based screening followed by medicinal chemistry and a structure-based design, we developed first-in-class small molecule inhibitors of the ASH1L SET domain.

Complexity of Blocking Bivalent Protein-Protein Interactions: Development of a Highly Potent Inhibitor of the Menin-Mixed-Lineage Leukemia Interaction.

The protein-protein interaction between menin and mixed-lineage leukemia 1 (MLL1) plays an important role in development of acute leukemia with translocations of the MLL1 gene and in solid tumors. Here, we report the development of a new generation of menin-MLL1 inhibitors identified by structure-based optimization of the thienopyrimidine class of compounds. This work resulted in compound 28 (MI-1481), which showed very potent inhibition of the menin-MLL1 interaction (IC = 3.

Design and Synthesis of Isoquinolidinobenzodiazepine Dimers, a Novel Class of Antibody-Drug Conjugate Payload.

Antibody-drug conjugates (ADCs) represent an important class of emerging cancer therapeutics. Recent ADC development efforts highlighted the use of pyrrolobenzodiazepine (PBD) dimer payload for the treatment of several cancers. We identified the isoquinolidinobenzodiazepine (IQB) payload (D211), a new class of PBD dimer family of DNA damaging payloads.

Pharmacologic Inhibition of the Menin-MLL Interaction Leads to Transcriptional Repression of and Blocks Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for approximately 85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein-protein interaction between menin and histone methyltransferase mixed lineage leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients.