The human ATP-binding cassette (ABC) transporters ABCB1, ABCC4 and ABCC5 are involved in resistance to chemotherapeutic agents. Here we present molecular models of ABCB1, ABCC4 and ABCC5 by homology based on a wide open inward-facing conformation of <i>Escherichia coli</i> MsbA, which were constructed in order to elucidate differences in the electrostatic and molecular features of their drug ...

Professor Svein Dahl ved Universitetet i Tromsø var en framtredende og nyskapende legemiddelforsker. De metodene han benyttet, brukes den dag i dag av farmasøytisk industri og forskere over hele verden.

<i>Background</i> - Clinical studies have reported overexpression of PDE5 and elevation of intracellular cyclic GMP in various types of cancer cells. ABCC5 transports cGMP out of the cells with high affinity. PDE5 inhibitors prevent both cellular metabolism and cGMP efflux by inhibiting ABCC5 as well as PDE5. Increasing intracellular cGMP is hypothesized to promote apoptosis and growth restriction ...

<p><i>Objectives</i>: To determine the ability of 11 sildenafil analogues to discriminate between cyclic nucleotide phosphodiesterases (cnPDEs) and to characterise their inhibitory potencies (<kursiv>K</kursiv>_i values) of PDE5A1‐dependent guanosine cyclic monophosphate (cGMP) hydrolysis.</p> <p><i>Methods</i>: Sildenafil analogues were identified by virtual ligand screening (VLS) ...

Intracellular cyclic nucleotides are eliminated by phosphodiesterases (PDEs) and by ATP Binding cassette transporters such as ABCC4 and ABCC5. PDE5 and ABCC5 have similar affinity for cGMP whereas ABCC5 has much higher affinity for cGMP compared with cAMP. Since the substrate (cGMP) is identical for these two eliminatory processes it is conceivable that various PDE inhibitors also modulate ...

The dominant sex hormone testosterone is mainly metabolized by liver enzymes belonging to the uridine-diphospho (UDP) glucuronosyltransferase (UGT) family. These enzymes are the main phase II enzymes, and they have an important role in the detoxification of endogenous and exogenous compounds in humans. The aim of the present study was to improve the understanding of the binding properties of UGT2B17. ...

Clinical data on the transfer of triptans into human breast milk remain scarce. In a lactation study including 19 breastfeeding women with migraine, we examined the excretion of six different triptans into milk. Following intake of a single dose, each participant collected seven breast milk samples at predefined intervals up to 24 hours after dose. Triptan concentrations in milk were measured using ...

<i>Introduction</i>: Cardiovascular dysfunction is a potentially lethal complication of hypothermia. Due to a knowledge gap, pharmacological interventions are not recommended at core temperatures below 30°C. Yet, further cooling is induced in surgical procedures and survival of accidental hypothermia is reported after rewarming from below 15°C, advocating a need for evidence-based treatment guidelines. ...