Towards streamlined product information: reporting of transporter-mediated drug interactions.

Purpose: The purpose of this study is to investigate the reporting of risks associated with transporter-mediated drug-drug interactions (DDIs) in medicinal product information and to identify suitable wording for future standardisation of summaries of product characteristics (SmPCs).

Methods: The SmPCs of medicinal products approved in the European Union from 2012 to 2023 were screened for warnings on Organic Anion Transporting Polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3), and Breast Cancer Resistance Protein (BCRP). An in-house search engine for product information was used.

In silico and biological analyses of missense variants of the human biliary efflux transporter ABCC2: effects of novel rare missense variants.

Background And Purpose: The ATP-dependent biliary efflux transporter ABCC2, also known as multidrug resistance protein 2 (MRP2), is essential for the cellular disposition and detoxification of various xenobiotics including drugs as well as endogenous metabolites. Common functionally relevant ABCC2 genetic variants significantly alter drug responses and contribute to side effects. The aim of this study was to determine functional consequences of rare variants identified in subjects with European ancestry using in silico tools and in vitro analyses.

Hepatic Expression of the Na-Taurocholate Cotransporting Polypeptide Is Independent from Genetic Variation.

The hepatic Na-taurocholate cotransporting polypeptide NTCP/ is important for the uptake of bile salts and selected drugs. Its inhibition results in increased systemic bile salt concentrations. NTCP is also the entry receptor for the hepatitis B/D virus.

Synthesis, Microtubule-Binding Affinity, and Antiproliferative Activity of New Epothilone Analogs and of an EGFR-Targeted Epothilone-Peptide Conjugate.

A new simplified, epoxide-free epothilone analog was prepared incorporating an N-(2-hydroxyethyl)-benzimidazole side chain, which binds to microtubules with high affinity and inhibits cancer cell growth in vitro with nM potency. Building on this scaffold, a disulfide-linked conjugate with the purported EGFR-binding (EGFR, epidermal growth factor receptor) peptide GE11 was then prepared. The conjugate retained significant microtubule-binding affinity, in spite of the size of the peptide attached to the benzimidazole side chain.

An imidazole based H-Phe-Phe-NH peptidomimetic with anti-allodynic effect in spared nerve injury mice.

The dipeptide amide H-Phe-Phe-NH (1) that previously was identified as a ligand for the substance P 1-7 (SP) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP and the tetrapeptide endomorphin-2 that is also binding to the SP site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration.