Pharmacogenetics - Drug Discovery Digest

Introduction to Pharmacogenetics

Broad Institute

MAY 30, 2024

Introduction to Pharmacogenetics By Rose Circeo May 30, 2024 Breadcrumb Home Introduction to Pharmacogenetics The Primer on Medical and Population Genetics is a series of weekly lectures on genetics topics related to human populations and disease.

Pharmacogenetics

Pharmacogenetics Bioethics Disease Research

Integrating pharmacogenetics data: a new lens for target prioritisation

The Open Targets Blog

MAY 9, 2024

In December 2023, we introduced the pharmacogenetics widget in the Open Targets Platform, which brings in data from PharmGKB on the influence of genetic variation on drug responses. Pharmacogenetics examines the link between genetics and drug response, helping in the prioritisation of drug targets that minimise the risk of adverse effects.

Pharmacogenetics

Pharmacogenetics Drugs Therapies Disease

Open Targets Platform 24.03 has been released!

The Open Targets Blog

MARCH 20, 2024

2023.12.016 Data updates Target safety We used pharmacogenetics data that informs about adverse drug response as an additional source of information on target safety. We have also introduced a pharmacogenetics widget integrating data from PharmGKB. DOI: 10.1016/j.ccell.2023.12.016 It was introduced in our 23.12

Pharmacogenetics

Pharmacogenetics Disease Drugs Research

Open Targets Platform 23.12 has been released!

The Open Targets Blog

NOVEMBER 30, 2023

Introducing pharmacogenetics data to the Platform This release introduces a new datasource to the Platform: the pharmacogenetics widget will incorporate data about the impact of human genetic variation on drug responses. You can find this data on the target and drug profile pages.

Pharmacogenetics

Pharmacogenetics Small Molecule Disease Drugs

The use-case for NGS

Drug Discovery World

OCTOBER 25, 2023

We can use NGS to better understand so-called “pharmacogenetics” so that we can predict how an individual may respond to a given treatment. This largely relates to the first question when I talked about pharmacogenetics and revealing and targeting specific mutations in an individual’s tumour. DG : For sure!

Bioinformatics

Bioinformatics Pharmacogenetics RNA Medical Schools

Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors [Metabolism, Transport, and Pharmacogenetics]

ASPET

APRIL 26, 2024

Histone deacetylase expression and activity are often dysregulated in central nervous system (CNS) tumors, providing a rationale for investigating histone deacetylase inhibitors (HDACIs) in selected brain tumor patients. Although many HDACIs have shown potential in in vitro studies, they have had modest efficacy in vivo.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Clinical Trials Trials

Pharmacokinetics of panobinostat: Inter-species difference in metabolic stability [Metabolism, Transport, and Pharmacogenetics]

ASPET

FEBRUARY 26, 2024

Panobinostat is a potent pan-HDAC inhibitor that has been tested in multiple studies for the treatment of brain tumors. There have been contrasting views surrounding its efficacy for the treatment of tumors in the CNS following systemic administration when examined in different models or species.

Metabolic Stability

Metabolic Stability Pharmacokinetics Pharmacogenetics Treatment

Characterization of hOAT4 and mOat5 as functional orthologs for renal anion uptake and efflux transport [Metabolism, Transport, and Pharmacogenetics]

ASPET

APRIL 16, 2024

Organic anions (OA) are compounds including drugs or toxicants that are negatively charged at physiological pH and are typically transported by Organic Anion Transporters (OATs). Human OAT4 (SLC22A11) is expressed in the apical membrane of renal proximal tubules.

Pharmacogenetics

Pharmacogenetics Drugs

Gene polymorphisms and drug-drug interactions determine the metabolic profile of blonanserin [Metabolism, Transport, and Pharmacogenetics]

ASPET

OCTOBER 20, 2023

This study aimed to evaluate the effects of cytochrome P450 3A4 (CYP3A4) gene polymorphism and drug interaction on the metabolism of blonanserin. Human recombinant CYP3A4 was prepared using the Bac-to-Bac baculovirus expression system.

Pharmacogenetics

Pharmacogenetics Drugs

Preclinical systemic pharmacokinetics, dose-proportionality, and CNS distribution of the ATM inhibitor WSD0628, a novel radiosensitizer for the treatment of brain tumors [Metabolism, Transport, and Pharmacogenetics]

ASPET

JUNE 10, 2024

Radiation therapy, a standard treatment option for many cancer patients, induces DNA double strand breaks (DSBs), leading to cell death. Ataxia telangiectasia mutated (ATM) kinase is a key regulator of DSB repair, and ATM inhibitors are being explored as radiosensitizers for various tumors, including primary and metastatic brain tumors.

Pharmacokinetics

Pharmacokinetics Pharmacogenetics Treatment DNA

CNS distribution of panobinostat in preclinical models to guide dosing for pediatric brain tumors [Metabolism, Transport, and Pharmacogenetics]

ASPET

OCTOBER 12, 2023

Achieving adequate exposure of a therapeutic agent at the target is a critical determinant of efficacious chemotherapy. With this in mind, a major challenge in developing therapies for central nervous system (CNS) tumors is to overcome barriers to delivery, including the blood-brain barrier (BBB).

Pharmacogenetics

Pharmacogenetics Clinical Trials Treatment Therapies

Humanization of SLCO2B1 in rats increases rCYP3A1 protein expression but not the metabolism of erlotinib to OSI-420 [Metabolism, Transport, and Pharmacogenetics]

ASPET

MARCH 6, 2024

The organic anion transporting polypeptide (OATP) 2B1 (gene name SLCO2B1 ) is an uptake transporter that facilitates cellular accumulation of its substrates. In order to assess the in vivo relevance of the transporter, we applied SLCO2B1 +/+ knock-in and Slco2b1 -/- knock-out rats.

Protein Expression

Protein Expression Pharmacogenetics Treatment Drugs

The Plasma Membrane Monoamine Transporter (PMAT) is Highly Expressed in Neuroblastoma and Functions as an mIBG Transporter [Metabolism, Transport, and Pharmacogenetics]

ASPET

AUGUST 4, 2023

Neuroblastoma (NB) is a pediatric cancer with low survival rates in high-risk patients. 131 I-mIBG has emerged as a promising therapy for high-risk NB and kills tumor cells by radiation. Consequently, 131 I-mIBG tumor uptake and retention are major determinants for its therapeutic efficacy.

Pharmacogenetics

Pharmacogenetics Therapies Disease

A Pilot Study to Assess the Suitability of Riboflavin as A Surrogate Marker of Breast Cancer Resistance Protein (BCRP) in Healthy Participants [Metabolism, Transport, and Pharmacogenetics]

ASPET

JANUARY 31, 2024

We recently showed that riboflavin is a selected substrate of BCRP over P-gp and demonstrated its prediction performance in preclinical DDI studies. The aim of this study was to investigate the suitability of riboflavin to assess BCRP inhibition in humans.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Drug Development Drugs

A personal touch: the role of bioprinting in drug discovery

Drug Discovery World

OCTOBER 5, 2022

This is where personalised drug screening and personalised treatment comes in because we can map pharmacogenetics, toxicity and drug metabolism of the active pharmaceutical ingredient for the particular individual. . Conventional drug discovery is a cumbersome process, as there are lots of stages to be tested with.

Pharmacogenetics

Pharmacogenetics Regulations Drugs Therapies

Significance of organic anion transporter 2 and organic cation transporter 2 in creatinine clearance: Mechanistic evaluation using freshly-prepared human primary renal proximal tubule cells [Metabolism, Transport, and Pharmacogenetics]

ASPET

NOVEMBER 17, 2023

Creatinine, a clinical marker for kidney function, is predominantly cleared by glomerular filtration, with active tubular secretion contributing to about 30% of its renal clearance.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Disease Drugs

Agena Bioscience Granted EUA for High-Throughput, Low-Cost SARS-CoV-2 Panel

The Pharma Data

OCTOBER 27, 2020

The system is a highly sensitive, cost-effective, mass spectrometry-based platform for high-throughput genetic analysis and is used globally in diverse research fields such as cancer profiling for solid tumors and liquid biopsies, inherited genetic disease testing, pharmacogenetics, agricultural genomics, and clinical research.

Pharmacogenetics

Pharmacogenetics Laboratories Clinical Research FDA

An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Observations [Metabolism, Transport, and Pharmacogenetics]

ASPET

AUGUST 4, 2023

The natural product goldenseal is a clinical inhibitor of CYP3A activity, as evidenced by a 40-60% increase in midazolam AUC after coadministration with goldenseal. The predominant goldenseal alkaloids berberine and (-)-β-hydrastine were previously identified as time-dependent CYP3A inhibitors using human liver microsomes.

Pharmacokinetics

Pharmacokinetics Pharmacogenetics Production Drugs

Diaceutics Launches World’s First Diagnostic Network for Precision Medicine to Solve Global Cancer Testing Issues

The Pharma Data

OCTOBER 27, 2020

Collaborators today include Synlab, PathGroup (US), SRL Diagnostics (Asia), Fundación Jimenez Díaz, The Royal Marsden NHS Foundation Trust, Istituto Nazionale Tumori Regina Elena Roma and Diatech Pharmacogenetics (EU). Two global pharmaceutical clients are also piloting the technology.

Pharmacogenetics

Pharmacogenetics Laboratories Therapies Hospitals

Drug Discovery Digest

Introduction to Pharmacogenetics

Integrating pharmacogenetics data: a new lens for target prioritisation

Trending Sources

Open Targets Platform 24.03 has been released!

Open Targets Platform 23.12 has been released!

The use-case for NGS

Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors [Metabolism, Transport, and Pharmacogenetics]

Pharmacokinetics of panobinostat: Inter-species difference in metabolic stability [Metabolism, Transport, and Pharmacogenetics]

Characterization of hOAT4 and mOat5 as functional orthologs for renal anion uptake and efflux transport [Metabolism, Transport, and Pharmacogenetics]

Gene polymorphisms and drug-drug interactions determine the metabolic profile of blonanserin [Metabolism, Transport, and Pharmacogenetics]

Preclinical systemic pharmacokinetics, dose-proportionality, and CNS distribution of the ATM inhibitor WSD0628, a novel radiosensitizer for the treatment of brain tumors [Metabolism, Transport, and Pharmacogenetics]

CNS distribution of panobinostat in preclinical models to guide dosing for pediatric brain tumors [Metabolism, Transport, and Pharmacogenetics]

Humanization of SLCO2B1 in rats increases rCYP3A1 protein expression but not the metabolism of erlotinib to OSI-420 [Metabolism, Transport, and Pharmacogenetics]

The Plasma Membrane Monoamine Transporter (PMAT) is Highly Expressed in Neuroblastoma and Functions as an mIBG Transporter [Metabolism, Transport, and Pharmacogenetics]

A Pilot Study to Assess the Suitability of Riboflavin as A Surrogate Marker of Breast Cancer Resistance Protein (BCRP) in Healthy Participants [Metabolism, Transport, and Pharmacogenetics]

A personal touch: the role of bioprinting in drug discovery

Significance of organic anion transporter 2 and organic cation transporter 2 in creatinine clearance: Mechanistic evaluation using freshly-prepared human primary renal proximal tubule cells [Metabolism, Transport, and Pharmacogenetics]

Agena Bioscience Granted EUA for High-Throughput, Low-Cost SARS-CoV-2 Panel

An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Observations [Metabolism, Transport, and Pharmacogenetics]

Diaceutics Launches World’s First Diagnostic Network for Precision Medicine to Solve Global Cancer Testing Issues

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