Continuous Positive Airway Pressure-Assisted Breathing With Supine Tangential Left Breast Radiation Therapy When Deep Inspiration Breath-Hold Radiation Therapy Was Ineffective or Unsuitable: Clinical Implications for an Affordable Heart-Sparing Breast Radiation Therapy to Reduce the Health Care Disparities in Low-Resource Settings.

Purpose: To report continuous positive airway pressure (CPAP)-assisted breathing with supine tangential left breast radiation therapy (CPAP-RT) when deep inspiration breath-hold RT (DIBH-RT) was ineffective or unsuitable.

Methods And Materials: Ten patients with left breast cancer underwent computed tomography simulation scan (CT-sim) under DIBH followed by CPAP-assisted breathing (15 cm HO) to create CPAP-RT plans in authors' institute. Reasons for CPAP-RT include inability to reproduce DIBH (n = 5), DIBH-RT plan exceeded dose limits to the heart (n = 2), and unable to proceed with planned DIBH-RT due to mechanical issues (n = 3).

Invention of MK-7845, a SARS-CoV-2 3CL Protease Inhibitor Employing a Novel Difluorinated Glutamine Mimic.

As SARS-CoV-2 continues to circulate, antiviral treatments are needed to complement vaccines. The virus's main protease, 3CLPro, is an attractive drug target in part because it recognizes a unique cleavage site, which features a glutamine residue at the P1 position and is not utilized by human proteases. Herein, we report the invention of MK-7845, a novel reversible covalent 3CLPro inhibitor.

Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia.

PDE10A is an important regulator of striatal signaling that, when inhibited, can normalize dysfunctional activity. Given the involvement of dysfunctional striatal activity with schizophrenia, PDE10A inhibition represents a potentially novel means for its treatment. With the goal of developing PDE10A inhibitors, early optimization of a fragment hit through rational design led to a series of potent pyrimidine PDE10A inhibitors that required further improvements in physicochemical properties, off-target activities, and pharmacokinetics.

A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells.

Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that can lead to eradication of persistent viral reservoirs in people living with HIV-1 (PLWH) remains an outstanding challenge to achieving cure. Utilizing a phenotypic screen, we identified a novel chemical class capable of killing HIV-1 infected peripheral blood mononuclear cells.

The identification of a novel lead class for phosphodiesterase 2 inhibition by fragment-based drug design.

We have identified a novel PDE2 inhibitor series using fragment-based screening. Pyrazolopyrimidine fragment 1, while possessing weak potency (K = 22.4 μM), exhibited good binding efficiencies (LBE = 0.