B. L. Roth

An shRNA screen in primary human beta cells identifies the serotonin 1F receptor as a negative regulator of survival during transplant

The paper identifies the serotonin 1F receptor as a negative regulator of human beta cell survival during transplant and demonstrates a small molecule antagonist that improves glycemia in islet transplants.

Structure-Based Discovery of a NPFF1R Antagonist with Analgesic Activity

This paper identifies a selective NPFF1R antagonist with analgesic properties, showing enhanced pain relief when combined with morphine and reduced side effects.

Nonspecific membrane bilayer perturbations by ivermectin underlie SARS-CoV-2 in vitro activity

This study shows ivermectin reduces SARS-CoV-2 viral burden in vitro but at concentrations that also cause cytotoxicity, suggesting its antiviral effect may be due to nonspecific membrane perturbation rather than specific antiviral activity.

The G protein biased serotonin 5-HT 2A receptor agonist lisuride exerts anti-depressant drug-like activities in mice

This study shows that lisuride, a G protein biased 5-HT2AR agonist, produces anti-depressant effects in mice without hallucinogenic actions, with limited involvement of β-arrestin pathways.

Neurotensin receptor allosterism revealed in complex with a biased allosteric modulator

This study reveals the cryoEM structures of NTSR1 with and without SBI-553, showing its biased allosteric modulation of G protein and β-Arrestin signaling.

Structural Genomics of the Human Dopamine Receptor System

This study reports cryo-EM structures of all human dopamine receptor subtypes bound to Rotigotine, revealing binding modes, activation mechanisms, and G-protein coupling specificity for drug design.

Structure-based Discovery of Conformationally Selective Inhibitors of the Serotonin Transporter

The paper identifies two novel inhibitors of the serotonin transporter that selectively target the inward-open conformation, showing improved potency and reduced off-target effects compared to existing drugs.

Structural insights into distinct signaling profiles of the μOR activated by diverse agonists

This study compares the structural and signaling differences between two μOR agonists, lofentanil and mitragynine pseudoindoxyl, revealing how their distinct binding modes lead to different G protein and β-arrestin activation profiles.

Structure-based design of a chemical probe set for the 5-HT5A serotonin receptor

The paper develops a more selective chemical probe set for the 5-HT5A receptor, showing improved selectivity and reduced assay liabilities compared to the existing SB-699551 antagonist.

Crystal structures of the σ2 receptor template large-library docking for selective chemotypes active in vivo

This study uses crystal structures of the σ2 receptor to dock and screen a large library, identifying new chemotypes with high affinity and selectivity for the receptor.

A novel mitragynine analog with low efficacy mu-opioid receptor agonism displays antinociception with attenuated adverse effects

The paper develops a novel mitragynine analog with reduced mu-opioid receptor efficacy and adverse effects, showing antinociception without respiratory depression or hyperlocomotion.