| 1. |
- Arvidsson, Per I., et al.
(författare)
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Open for collaboration : an academic platform for drug discovery and development at SciLifeLab
- 2016
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 21:10, s. 1690-1698
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Forskningsöversikt (refereegranskat)abstract
- The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform, and reflect on our first two years of operation, with the ambition to share learnings and best practice with academic drug discovery centers globally. We also discuss how the Swedish Teacher Exemption Law, an internationally unique aspect of the innovation system, has shaped the operation. Furthermore, we address how this investment in infrastructure and expertise can be utilized to facilitate international collaboration between academia and industry in the best interest of those ultimately benefiting the most from translational pharmaceutical research - the patients.
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| 2. |
- Bersani, Francesco S, et al.
(författare)
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Telomerase activation as a possible mechanism of action for psychopharmacological interventions.
- 2015
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 20:11, s. 1305-1309
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Forskningsöversikt (refereegranskat)abstract
- Originally studied in relation to aging and cancer research, telomerase is now also investigated in relation to psychiatric disorders and treatments. Based on emerging clinical and preclinical data, we hypothesise that telomerase activation could represent a novel element mediating the mechanism of action of certain psychopharmacological interventions (e.g. antidepressants, lithium and antipsychotics). The modulation of intracellular Wnt/β-catenin or PI3K/Akt signalling pathways, the interaction with BDNF and 5-HT, and the antioxidant properties could represent possible mechanisms by which the different types of psychiatric medications could modulate telomerase activity. The potential of telomerase in promoting cellular survival and/or function in the brain and in the periphery could, in turn, represent a neurobiological substrate through which the enzyme can mediate the therapeutic effect of such interventions.
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| 3. |
- Bignami, Francesca, et al.
(författare)
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Potential effects of increased openness in pharma : the original knowledge behind new drugs
- 2019
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832.
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Tidskriftsartikel (refereegranskat)abstract
- This study seeks to determine potential changes in the degree of openness in pharmaceutical R&D by investigating where the knowledge behind new molecular entities (NMEs) comes from in terms of type of organization, geography and time. We find that the organizations granted NMEs increasingly rely on external knowledge sources but that these are increasingly shared among NME grantees. Universities are the most important indirect knowledge contributor and their relative importance has increased with time. NME grantees are increasingly relying on knowledge from different countries and the age of the knowledge sources confirms that recent NMEs are mostly follow-on drugs. This work provides evidence of the increasing openness of pharma to new knowledge sources as a means to improving the drug discovery and development process.
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| 4. |
- Colcloughl, Nicola, et al.
(författare)
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Building on the success of osimertinib : achieving CNS exposure in oncology drug discovery
- 2019
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 24:5, s. 1067-1073
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Forskningsöversikt (refereegranskat)abstract
- Due to the blood-brain barrier (BBB) limiting the exposure of therapeutics to the central nervous system (CNS), patients with brain malignancies are challenging to treat, typically have poor prognoses, and represent a significant unmet medical need. Preclinical data report osimertinib to have significant BBB penetration and emerging clinical data demonstrate encouraging activity against CNS malignancies. Here, we discuss the oncology drug candidates AZD3759 and AZD1390 as case examples of discovery projects designing in BBB penetrance. We demonstrate how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders.
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| 5. |
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| 6. |
- Hering, Jenny, et al.
(författare)
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Structural basis for selective inhibition of antibacterial target MraY, a membrane-bound enzyme involved in peptidoglycan synthesis
- 2018
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 23:7, s. 1426-1435
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Forskningsöversikt (refereegranskat)abstract
- The rapid growth of antibiotic-resistant bacterial infections is of major concern for human health. Therefore, it is of great importance to characterize novel targets for the development of antibacterial drugs. One promising protein target is MraY (UDP-N-acetylmuramyl-pentapeptide: undecaprenyl phosphate N-acetylmuramyl-pentapeptide-1-phosphate transferase or MurNAc-1-P-transferase), which is essential for bacterial cell wall synthesis. Here, we summarize recent breakthroughs in structural studies of bacterial MraYs and the closely related human GPT (UDP-N-acetylglucosamine: dolichyl phosphate N-acetylglucosamine-1-phosphate transferase or GlcNAc-1-P-transferase). We present a detailed comparison of interaction modes with the natural product inhibitors tunicamycin and muraymycin D2. Finally, we speculate on possible routes to design an antibacterial agent in the form of a potent and selective inhibitor against MraY.
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| 7. |
- Holgersson, Marcus, 1983, et al.
(författare)
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Entrepreneurial patent management in pharmaceutical startups
- 2016
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 21:7, s. 1042-1045
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Tidskriftsartikel (refereegranskat)abstract
- Startups fill an increasingly important role as innovators in the pharmaceutical industry, and patenting is typically central to their success. This article aims to explore patent management in pharmaceutical startups. The results show that startups need to deal with several challenges related to patenting and an ‘entrepreneurial’ approach to patent management is called for. Resource constraints, venture capital provision, exits and other conditions and events must be readily considered in the patent management process to build a successful pharmaceutical venture, something that could benefit the pharmaceutical industry as a whole.
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| 8. |
- Karlsson, Jan Olof G, et al.
(författare)
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Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties.
- 2015
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 20:4, s. 411-421
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Forskningsöversikt (refereegranskat)abstract
- Reactive oxygen species (ROS) and reactive nitrogen species (RNS) participate in pathological tissue damage. Mitochondrial manganese superoxide dismutase (MnSOD) normally keeps ROS and RNS in check. During development of mangafodipir (MnDPDP) as a magnetic resonance imaging (MRI) contrast agent, it was discovered that MnDPDP and its metabolite manganese pyridoxyl ethyldiamine (MnPLED) possessed SOD mimetic activity. MnDPDP has been tested as a chemotherapy adjunct in cancer patients and as an adjunct to percutaneous coronary intervention in patients with myocardial infarctions, with promising results. Whereas MRI contrast depends on release of Mn(2+), the SOD mimetic activity depends on Mn(2+) that remains bound to DPDP or PLED. Calmangafodipir [Ca4Mn(DPDP)5] is stabilized with respect to Mn(2+) and has superior therapeutic activity. Ca4Mn(DPDP)5 is presently being explored as a chemotherapy adjunct in a clinical multicenter Phase II study in patients with metastatic colorectal cancer.
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| 9. |
- Molavipordanjani, Sajjad, et al.
(författare)
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Basic and practical concepts of radiopharmaceutical purification methods
- 2019
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Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 24:1, s. 315-324
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Forskningsöversikt (refereegranskat)abstract
- The presence of radiochemical impurities in a radiopharmaceutical contributes to an unnecessary radiation burden for the patients or to an undesirable high radioactivity background, which reduces the imaging contrast or therapeutic efficacy. Therefore, if the radiolabeling process results in unsatisfactory radiochemical purity, a purification step is unavoidable. A successful purification process requires a profound knowledge about the radiopharmaceuticals of interest ranging from structural features to susceptibility to different conditions. Most radiopharmaceutical purification methods are based on solid phase extraction (SPE), high-performance liquid chromatography (HPLC), size exclusion chromatography (SEC), ion-exchange chromatography (IEC), and liquid-liquid extraction (LLE). Here, we discuss the basic and applied concepts of these purifications methods as well as their advantages and limitations.
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| 10. |
- Muliaditan, Morris, et al.
(författare)
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The implications of model-informed drug discovery and development for tuberculosis
- 2017
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Ingår i: Drug Discovery Today. - : ELSEVIER SCI LTD. - 1359-6446 .- 1878-5832. ; 22:3, s. 481-486
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Forskningsöversikt (refereegranskat)abstract
- Despite promising advances in the field and highly efficacious first-line treatment, an estimated 9.6 million people are still infected with tuberculosis (TB). Innovative methods are required to effectively transition the growing number of compounds into novel combination regimens. However, progression of compounds into patients occurs despite the lack of clear understanding of the pharmacokineticpharmacodynamic (PKPD) relationships. The PreDiCT-TB consortium was established in response to the existing gaps in TB drug development. The aim of the consortium is to develop new preclinical tools in concert with an in silico model-based approach, grounded in PKPD principles. Here, we highlight the potential impact of such an integrated framework on the various stages of TB drug development and on the dose rationale for drug combinations.
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