PROTAC: targeted drug strategy. Principles and limitations.

The PROTAC () technology is a method of targeting intracellular proteins previously considered undruggable. This technology utilizes the ubiquitin-proteasome system in cells to specifically degrade target proteins, thereby offering significant advantages over conventional small-molecule inhibitors of the enzymatic function. Preclinical and preliminary clinical trials of PROTAC-based compounds (degraders) are presented.

Design and Characterization of Novel Small Molecule Activators of Excitatory Amino Acid Transporter 2.

Excitotoxicity in the brain is a causal factor in several neurological and neurodegenerative disorders. Excitatory amino acid transporter 2 (EAAT2), an astrocytic glutamate transporter involved in the clearance of >80% of synaptic glutamate, is considered a therapeutically relevant target for excitotoxicity. We have previously designed GT951, an activator of EAAT2 with nanomolar efficacy but limited in vivo bioavailability.

Incidence Rate and Risk Factors for Tuberculosis among People Living with HIV: A 2015-2017 Cohort from Tashkent, Uzbekistan.

People living with the human immunodeficiency virus (PLHIV) have a higher risk of developing active tuberculosis (TB) disease, and TB remains a major cause of death in PLHIV. Uzbekistan is facing a substantial TB epidemic, which increases the risk of PLHIV developing active TB. Our retrospective cohort study aimed to evaluate the incidence rate and assess the risk factors for developing active TB among PLHIV.

Effectiveness and Safety of a Shorter Treatment Regimen in a Setting with a High Burden of Multidrug-Resistant Tuberculosis.

Treatment of drug-resistant tuberculosis is lengthy, insufficiently effective, and toxic. Since 2016, the World Health Organization has recommended shorter treatment regimens (STR). We assessed effectiveness and predictors of drug adverse events (DAE) among patients treated with STR.

Absence of APP713 mutation in Italian and Russian families with schizophrenia.

A recent study has shown a mutation at codon 713 of the amyloid precursor protein (APP) gene in a schizophrenic patient. We have analyzed the MaeIII restriction site caused by that mutation in Italian and Russian families with schizophrenia. No mutations were observed suggesting that the APP713 mutation is unlikely to be linked to the pathogenesis of such a psychiatric disorder.