Insights into Transporter Classifications: an Outline of Transporters as Drug Targets

Viereck, Michael; Gaulton, Anna; Digles, Daniela

doi:10.1002/9783527679430.ch1

Cited by 2 publications

(1 citation statement)

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“…The area under the curve of Organic Anionic Transporter 2B1 (OATP2B1) substrates decreased almost two-fold due to grapefruit juice, an OATP2B1 inhibitor ( Zamek-Gliszczynski et al, 2018 ). Approved drugs targeting cell membrane transport protein are numerous and include: solute carriers (Fluoxetin, Furosemide), ATPases (Omeprazol, Digitoxin), and ABC binding cassette (Ivacaftor, Repaglinide) amongst others ( Viereck et al, 2017 ) Exploiting transporters can have potent effects on the cells of the human body. There already exists evidence that transporters play a greater role in drug uptake than originally thought.…”

Section: Introduction–drug Developmentmentioning

confidence: 99%

Cell Surface Transporters and Novel Drug Developments

Carmichael

Day

2022

Front. Pharmacol.

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Despite the numerous scientific and technological advances made within the last decade the attrition rates for new drug discovery remain as high as 95% for anticancer drugs. Recent drug development has been in part guided by Lipinski’s Rule of 5 (Ro5) even though many approved drugs do not comply to these rules. With Covid-19 vaccine development strategy dramatically accelerating drug development perhaps it is timely to question the generic drug development process itself to find a more efficient, cost effective, and successful approach. It is widely believed that drugs permeate cells via two methods: phospholipid bilayer diffusion and carrier mediated transporters. However, emerging evidence suggests that carrier mediated transport may be the primary mechanism of drug uptake and not diffusion as long believed. Computational biology increasingly assists drug design to achieve desirable absorption, distribution, metabolism, elimination and toxicity (ADMET) properties. Perfecting drug entry into target cells as a prerequisite to intracellular drug action is a logical and compelling route and is expected to reduce drug attrition rates, particularly gaining favour amongst chronic lifelong therapeutics. Novel drug development is rapidly expanding from the utilisation of beyond the rule of five (bRo5) to pulsatile drug delivery systems and fragment based drug design. Utilising transporters as drug targets and advocating bRo5 molecules may be the solution to increasing drug specificity, reducing dosage and toxicity and thus revolutionising drug development. This review explores the development of cell surface transporter exploitation in drug development and the relationship with improved therapeutic index.

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Section: Introduction–drug Developmentmentioning

confidence: 99%