Drugs and Pharmacogenetics - Drug Discovery Digest

Open Targets Platform 24.03 has been released!

The Open Targets Blog

MARCH 20, 2024

The team identified 370 priority drug targets for 27 cancer types in a truly data-driven approach, leveraging clinical-relevant transcriptional signatures, metabolic and proteomics data, protein-protein interaction networks and more. In addition, we now indicate whether a target is a direct target of the drug. DOI: 10.1016/j.ccell.2023.12.016

Pharmacogenetics

Pharmacogenetics Disease Drugs Research

Open Targets Platform 23.12 has been released!

The Open Targets Blog

NOVEMBER 30, 2023

Target prioritisation A major new feature of this release is the Target Prioritisation view, which provides an assessment of target-specific properties of interest when evaluating the suitability of a target for a drug discovery programme. It is presented here with an additional layer of analysis with a drug discovery focus.

Pharmacogenetics

Pharmacogenetics Small Molecule Disease 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. A microsomal enzyme reaction system was established, and drug-drug interactions were evaluated using Sprague-Dawley rats. Clearance of blonanserin by CYP3A4.4,

Pharmacogenetics

Pharmacogenetics Drugs

A personal touch: the role of bioprinting in drug discovery

Drug Discovery World

OCTOBER 5, 2022

DDW Editor, Reece Armstrong, sits down with Brinter CEO Tomi Kalpio to learn about the company’s approach to bioprinting and how it can be used throughout drug discovery. . RA: How can bioprinting be used to shorten drug discovery timelines? . This allows researchers to identify the best individual drugs to treat the disease. .

Pharmacogenetics

Pharmacogenetics Regulations Drugs Therapies

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

ASPET

APRIL 26, 2024

This lack of activity could be due to insufficient CNS exposure to the unbound drug. Although many HDACIs have shown potential in in vitro studies, they have had modest efficacy in vivo. Both compounds undergo in vitro degradation in mouse plasma, requiring precautions during sample processing.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Clinical Trials Trials

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

ASPET

FEBRUARY 26, 2024

This lack of translation between in vitro metabolism assays and in vivo disposition can confound drug development. This suggests that the inter-strain difference in enzymatic activity did not affect the in vivo pharmacokinetic behavior of panobinostat and its CNS distribution in mice.

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). For the profile of OTA inhibition by OAs, IC 50 values were determined for several clinically important drugs and toxicants. pmol/cm 2 , respectively.

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

Efficacy of radiosensitizers for brain tumors may be influenced by a lack of effective drug delivery across the blood-brain barrier (BBB). 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

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. Different predicted functional consequences of pharmacogenetics variants from the PharmGKB data. What's new?

Pharmacogenetics

Pharmacogenetics Drugs 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

First, we assessed the substrate potential of riboflavin towards other major drug transporters using established transfected cell systems. Overall, these data indicate that plasma riboflavin is a promising biomarker of BCRP that may offer a possibility to assess drug candidate as a BCRP modulator in early drug development.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Drug Development Drugs

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

Quantitative pharmacokinetic models should therefore focus on OCT2/MATE when describing serum creatinine and creatinine clearance modulation by inhibitor drugs and genotype- or disease-related activity changes.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Disease Drugs

The use-case for NGS

Drug Discovery World

OCTOBER 25, 2023

DDW Editor Reece Armstrong speaks to Dr Darrell Green , Lecturer in RNA Biology Biomedical Research Centre Norwich Medical School University of East Anglia, about his work using next generation sequencing (NGS) and the areas the technology is impacting within drug discovery and development. DG : For sure!

Bioinformatics

Bioinformatics Pharmacogenetics RNA Medical Schools

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

A first pharmacological phenotyping with the OATP2B1 substrate-drug atorvastatin revealed reduced hepatic content and increased expression of rCYP3A1 in the humanized animals. 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

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

Results highlight the potential interplay between time-dependent and reversible inhibition of intestinal CYP3A as the mechanism underlying natural product-drug interactions, even after acute exposure to the precipitant.

Pharmacokinetics

Pharmacokinetics Pharmacogenetics Production Drugs

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

The Pharma Data

OCTOBER 27, 2020

Food and Drug Administration (FDA). SAN DIEGO , Oct. Clinical laboratories can process thousands of samples each day for less than $10 per sample running the assay on a single MassARRAY instrument, making it one of the highest throughput SARS-CoV-2 tests available under the Emergency Use Authorization program. SOURCE Agena Bioscience.

Pharmacogenetics

Pharmacogenetics Laboratories Clinical Research FDA

Drug Discovery Digest

Open Targets Platform 24.03 has been released!

Open Targets Platform 23.12 has been released!

Trending Sources

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

A personal touch: the role of bioprinting in drug discovery

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]

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]

Integrating pharmacogenetics data: a new lens for target prioritisation

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]

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]

The use-case for NGS

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

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]

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

Stay Connected