Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2.

Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds , , and ) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of and were chemically modified.

Tankyrase-selective inhibitor STP1002 shows preclinical antitumour efficacy without on-target toxicity in the gastrointestinal tract.

Background: Tankyrase inhibition stabilises AXINs and antagonises the Wnt/β-catenin pathway in adenomatous polyposis coli (APC)-mutated colorectal cancer (CRC), suggesting that tankyrase is a potential therapeutic target for APC-mutated CRC. However, clinical trials on reported tankyrase inhibitors have been severely limited by on-target toxicity in the gastrointestinal (GI) tract. Herein, we report a new tankyrase-selective inhibitor, STP1002, having preclinical antitumour efficacy without on-target toxicity in APC-mutated CRC models.

Anticoagulation therapy promotes the tumor immune-microenvironment and potentiates the efficacy of immunotherapy by alleviating hypoxia.

Purpose: Here, this study verifies that cancer-associated thrombosis (CAT) accelerates hypoxia, which is detrimental to the tumor immune microenvironment by limiting tumor perfusion. Therefore, we designed an oral anticoagulant therapy to improve the immunosuppressive tumor microenvironment and potentiate the efficacy of immunotherapy by alleviating tumor hypoxia.

Experimental Design: A novel oral anticoagulant (STP3725) was developed to consistently prevent CAT formation.

A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site.

Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction.

Comparison of Antiviral Activity of Gemcitabine with 2'-Fluoro-2'-Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. The virus still spreads globally through human-to-human transmission. Nevertheless, there are no specific treatments clinically approved.

Folding and anion-binding properties of fluorescent oligoindole foldamers.

A series of oligoindole foldamers 1 a-d that are highly fluorescent were prepared by using a biindole derivative as the repeating unit, and their folding and anion-binding properties were revealed by (1)H NMR and fluorescence spectroscopy. The oligoindoles exist in an extended conformation, but adopt a compact helical structure in the presence of an anion. The anion is entrapped inside the tubular cavity of the helical strand, comprising four aryl units per turn, by multiple hydrogen bonds with the indole NHs.