Xi‐Ping Huang

The selectivity implications of docking libraries with greater and lesser similarities to bio-like molecules

The paper tests if molecules from ultra-large libraries are more selective than those from bio-like libraries, finding similar off-target activity despite differences in chemical novelty.

The polypharmacological profiles of xanomeline and N-desmethylxanomeline

This study investigates the polypharmacological profiles of xanomeline and its metabolite N-desmethylxanomeline, revealing their agonist and antagonist actions at multiple biogenic amine G protein-coupled receptors.

Xylazine's k-opioid agonist activity is not shared with other FDA-approved alpha2-adrenergic agonists

The paper investigates whether other FDA-approved alpha2-adrenergic agonists share xylazine's kappa opioid agonist activity and finds they do not, but have distinct GPCR activity patterns.

Differential effects of sodium on agonist-induced conformational transitions and signaling at μ and κ opioid receptors

The paper examines how sodium ions differentially modulate agonist-induced conformational changes and signaling at μ and κ opioid receptors, revealing opposing effects between the two receptor types.

Molecular basis of proton-sensing by G protein-coupled receptors

The paper identifies proton-sensing mechanisms in GPCRs using cryo-EM and deep mutational scanning, revealing a network of residues rather than a single site for proton recognition.

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.

Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to naloxone administration

This study shows xylazine acts as a kappa opioid receptor agonist and that naloxone induces withdrawal from xylazine and fentanyl/xylazine combinations, with greater sensitivity in females.

De Novo Design of κ-Opioid Receptor Antagonists Using a Generative Deep Learning Framework

This study uses a generative deep learning framework to design new KOR antagonists, which are prioritized for synthesis and validated through experimental assays.

Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor

The paper reports the structures of D1R-Gs complex bound to dopamine and LY3154207, revealing mechanisms of dopamine recognition and allosteric modulation for drug discovery.

Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys

This paper introduces deschloroclozapine (DCZ), a potent and selective DREADD agonist that rapidly modulates neuronal activity and behavior in mice and monkeys.

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Affinity-purification mass spectrometry of 26 SARS-CoV-2 proteins in HEK293T cells yields 332 high-confidence host interactions and 67 druggable human proteins with known compounds.

PHARMACOLOGY OF W-18 AND W-15

This study investigates the pharmacological profiles of W-18 and W-15, finding no significant opioid activity or other psychoactive drug target interactions.

A Simple Representation Of Three-Dimensional Molecular Structure

This paper introduces a 3D molecular representation (E3FP) that improves drug-to-target prediction compared to 2D fingerprints, with experimental validation of novel binding predictions.