Pharmacogenetics and Drug Metabolism

Characterization of the Preclinical in Vitro and in Vivo Pharmacokinetic Properties of the Cyclic Oligomeric Depsipeptide Ryanodine Receptor 2 Inhibitor ent-Verticilide

This study characterizes the pharmacokinetic properties of ent-verticilide, identifying limited intestinal availability and CYP-mediated metabolism as key factors affecting its oral exposure.

CyriPanel for CYP2D6 Genotyping from Targeted Capture Panels Using Assay-Matched Diploid References

CyriPanel improves CYP2D6 genotyping accuracy using assay-matched diploid references and structural inference, achieving higher concordance than Aldy 4 in benchmark tests.

Primary Human Macrophages Exhibit Functional CYP3A4 Activity with Marked Expression-Function Discordance and Cocaine-Induced Catalytic Activation

This study shows human macrophages have functional CYP3A4 activity, with expression and function discordance, and cocaine increases CYP3A4 activity across donors.

Human CYP1A2 metabolism of organophosphorus pesticides and nerve agent surrogates

This study investigates CYP1A2's role in metabolizing organophosphorus compounds and finds it selectively degrades thions and is inhibited by OP compounds, suggesting its potential as a bioscavenger.

Liver Fatty Acid Binding Protein (FABP1) Affects Cytochrome P450 2C9 (CYP2C9)-Mediated Metabolism in Human Liver Models

The paper shows that FABP1 affects CYP2C9-mediated drug metabolism in human liver models, improving prediction accuracy when included in physiologically based models.

Characterization of Cytochrome P450-Mediated Metabolism of Δ8-tetrahydrocannabinol in vitro

This study identifies the main cytochrome P450 enzymes responsible for metabolizing Δ8-THC in human liver microsomes and shows that CYP2C9 is the primary catalyst for its 11-hydroxylation.

Intermolecular interactions of CYP3A enzymes and cytosolic sulfotransferases (SULT1E1, SULT2A1)

This study identifies direct physical interactions between CYP3A4/3A5 and SULT1E1/2A1 using SPR, activity assays, and AlphaFold2 modeling, revealing potential substrate channeling mechanisms.

Human prostaglandin reductases dearomatize and inactivate benzothiazinone antitubercular drugs

The paper shows human prostaglandin reductases PTGR1 and PTGR2 inactivate the antitubercular drug MCZ by dearomatizing it into H2MCZ, reducing its antimycobacterial activity.

Homology-Based Variant-Effect Predictors Break Down on Cytochrome P450 Pharmacogenes

The paper shows homology-based variant-effect predictors fail for CYP enzymes and proposes an improved model that still lacks clinical relevance.

AetherXeno: an allele-resolved receptor-occupancy atlas for regulatory pharmacogenomics

AetherXeno provides an allele-resolved receptor-occupancy atlas linking pharmacogenomic variants to regulatory elements, improving correlation with experimental data.

Structural Plasticity and Ligand Promiscuity of CYP3A4 Revealed by Cryo-EM

This study uses cryo-EM to reveal structural plasticity and ligand promiscuity of CYP3A4, showing multiple conformations and highlighting the F/G loop's role in binding pocket remodeling.

Cryo-EM structure of CYP2C9 reveals a dimer-of-trimers assembly

The paper reports the cryo-EM structure of CYP2C9, revealing a dimer-of-trimers assembly and its stabilization mechanisms.

A Curated Pharmacogenomic Allele Catalog for Sub-Saharan African Populations

The paper curates a pharmacogenomic allele catalog for Sub-Saharan African populations, highlighting population-specific frequencies and functional annotations for six pharmacogenes.

Pediatric pharmacogenomics from whole-exome sequencing: developmentally appropriate interpretation in 1,159 Russian children and newborns

This study evaluates pharmacogenomic data in Russian children and newborns, highlighting the need for age-adjusted interpretation and developing a pediatric pharmacogenomics reporting model.

preSCRIPT: Large-scale prescription search and annotation engine for pharmacogenomic studies

preSCRIPT filters and annotates prescription data from UK Biobank to derive drug response phenotypes, replicating known PGx associations and identifying novel candidates.

Introduction to Single-cell Physiologically-Based Pharmacokinetic (scPBPK) Models

This paper introduces scPBPK models to study drug disposition at the cellular level, showing heterogeneity in drug concentration using negative binomial distributions for ED processes.

In-silico functional prediction of novel tuberculosis pharmacogenetic variants and NAT2 phenotype prediction in African populations

The paper predicts NAT2 genotypes and phenotypes in African populations using bioinformatic tools and next-generation sequencing data to inform pharmacogenetic treatment strategies for tuberculosis.

Comparative evaluation of genotyping and low-pass sequencing for pharmacogenetic variant and phenotype inference

This study compares genotyping arrays and low-pass whole-genome sequencing for pharmacogenetic variant and phenotype inference, finding high concordance but improved variant coverage with LP-WGS.

Genotype-predicted drug response phenotypes and their co-occurrence with dispensed medicines among 738,531 participants in the UK Our Future Health study

The paper assesses the co-occurrence of actionable pharmacogenomic phenotypes with dispensed medicines in 738,531 UK participants, finding 36.8% had gene-matched medications.

The role of CYP3A-CYP2E1 interactions in activation of CYP3A enzymes by chronic alcohol exposure

This study investigates how chronic alcohol exposure increases CYP3A enzyme activity in human liver microsomes through interactions with CYP2E1, despite no change in CYP3A levels.

Large-scale analysis demonstrates the influence of CYP2C19 genotype on specific SSRI side effects

The paper analyzes the impact of CYP2C19 genotype on SSRI side effects and discontinuation rates in a large sample of individuals.

Pseudomonas aeruginosa co-opts host antibiotic metabolism by pyocyanin induction of cytochrome P450 enzymes

This study shows that Pseudomonas aeruginosa induces CYP1A2 expression via pyocyanin, increasing ciprofloxacin metabolism and potentially reducing antibiotic efficacy.

Critically Ill Children Frequently Receive Medications with Established but Unused Pharmacogenomic Guidelines: Actionable Findings from an Integrated Electronic Medical Record and Exome Sequencing Study

This study finds that many critically ill children receive medications with established pharmacogenomic guidelines, but exome sequencing identifies actionable PGx variants that could improve treatment.

Expanding the GUSome: Structure-guided identification and characterization of gut microbial β-glucuronidases

This study identifies and characterizes 79 unique gut microbial β-glucuronidases using structural modeling and classification based on domain architecture and substrate preferences.

Chemical augmentation of the validated HepaRGTM CYP induction test method Part 2: Additional laboratory study supported by mRNA analysis

A third laboratory transferred the HepaRG CYP induction assay to six augmentation and four additional non-pharmaceutical chemicals; parallel mRNA data supported enzyme activity calls, with CYP3A4 most concordant.

Chemical augmentation of the validated HepaRGTM CYP enzyme induction test method Part 1: The Goliath two laboratory study

This paper validates the HepaRG CYP enzyme induction test method for pharmaceutical and non-pharmaceutical chemicals, showing good reproducibility for pharmaceuticals but less consistency for non-pharmaceuticals.

Global population frequencies of NAT2 star alleles observed in three large biobanks

The paper reports NAT2 star allele frequencies across three biobanks, identifying common alleles and population-specific differences in metabolizer phenotypes.

Evaluating the Clinical Impact of CYP2C19 and CYP2D6 on Amitriptyline Outcomes in a Real-World Chronic Pain Cohort

This study examines the association between CYP2C19 and CYP2D6 metabolizer phenotypes and amitriptyline effectiveness and tolerability in a chronic pain cohort, finding no strong associations after correction for multiple testing.

Convergent gene erosion in the chemical defensome of marine mammals

The paper identifies convergent gene loss in the chemical defensome across marine mammals, highlighting adaptation to aquatic environments and reduced detoxification capacity.

Pharmacokinetic Acceleration via CYP3A4 Hyperactivation as a Clinically Actionable Mechanism of Targeted Therapy Resistance in NSCLC

This paper identifies CYP3A4 hyperactivation as a tumor-extrinsic resistance mechanism in NSCLC, showing it reduces drug exposure and leads to resistance, and proposes dosing optimization and CYP3A4 inhibition as solutions.