| 1. |
- Tulp, Martin, et al.
(författare)
-
Functional versus chemical diversity: is biodiversity important for drug discovery?
- 2002
-
Ingår i: TIPS - Trends in Pharmacological Sciences. - 0165-6147 .- 1873-3735. ; 23:5, s. 225-231
-
Tidskriftsartikel (refereegranskat)abstract
- Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less. It is likely that many millions of chemically distinct molecules exist in nature but it is inconceivable that the number of different biological functions is near this number. This is corroborated by knowledge obtained from the genome sequences of an increasing number of species. It is unlikely that ligands for specific molecular targets are restricted to one species and even individual compounds are often found in more than one species. Important molecular mechanisms are likely to be ubiquitous and there are no a priori reasons to assume that some are restricted to, for example, tropical rainforests. Thus, there are no obvious advantages of ‘biodiversity prospecting’, which will, possibly, endanger fragile ecosystems in the search for rare species.
|
|
| 2. |
- Arnberg, Niklas
(författare)
-
Adenovirus receptors : implications for targeting of viral vectors
- 2012
-
Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier. - 0165-6147 .- 1873-3735. ; 33:8, s. 442-448
-
Forskningsöversikt (refereegranskat)abstract
- Cancer, cardiovascular disease, and infectious diseases are all global health threats. To combat these diseases with gene therapies, adenovirus-based vectors have been developed. Although certain clinical trials appear successful, there is an obvious need to improve the efficacy of most adenovirus-based vectors. For the most commonly used vector (based on type 5; Ad5), a main problem is its accumulation in the liver, which can be attributed to interactions with specific host factors. The diverse tropism for types other than Ad5 implies that vectors based on alternative types could have advantages. The numerous interactions of different adenoviruses with host molecules - such as the recently identified desmoglein-2 receptor - may cause novel and unexpected obstacles, but also may provide possibilities for vectors based on alternative types. This review provides an update of new and previously known molecules that mediate cellular attachment of human adenoviruses and discusses how these may influence the targeting of adenovirus-based vectors.
|
|
| 3. |
- Attwood, Misty M., et al.
(författare)
-
Orphan Drugs and Their Impact on Pharmaceutical Development
- 2018
-
Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 39:6, s. 525-535
-
Forskningsöversikt (refereegranskat)abstract
- High levels of productivity, with an increasing number of approvals for new molecular entities (NMEs) by the FDA during the past decade, have coincided with the emergence of innovative drugs for treatments of rare diseases that have utilized the FDA orphan drug program. Since 2000, NMEs with orphan designation encompass a significant portion of approved drugs and constitute about 80% of the approved drugs that have established novel human genome-encoded products in recent years. Biological approvals are also expanding, with 40% of the approved biological agents having orphan designation. This trend illustrates a pivot within the pharmaceutical industry: from research programs that focus on canonical blockbuster indications and targets, towards the establishment of new treatments for rare and difficult to treat diseases.
|
|
| 4. |
|
|
| 5. |
- Baijnath, Sooraj, et al.
(författare)
-
Advances in spatial mass spectrometry enable in-depth neuropharmacodynamics
- 2022
-
Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier. - 0165-6147 .- 1873-3735. ; 43:9, s. 740-753
-
Forskningsöversikt (refereegranskat)abstract
- Mass spectrometry imaging (MSI) is a powerful technique that combines the abil-ity of microscopy to provide spatial information about multiple molecular species with the specificity of mass spectrometry (MS) for unlabeled mapping of analytes in diverse biological tissues. Initial pharmacological applications focused on drug distributions in different organs, including the compartmentalized brain. However, recent technological advances in instrumentation, software, and chemical tools have allowed its use in quantitative spatial omics. It now enables visualization of distributions of diverse molecules at high lateral resolution in studies of the pharmacokinetic and neuropharmacodynamic effects of drugs on functional biomolecules. Therefore, it has become a versatile technique with a multitude of applications that have transformed neuropharmacological re-search and enabled research into brain physiology at unprecedented resolution, as described in this review.
|
|
| 6. |
- Banerjee, Debarshi, et al.
(författare)
-
Adding nanotechnology to the metastasis treatment arsenal
- 2019
-
Ingår i: TIPS - Trends in Pharmacological Sciences. - Cambridge, Massachusets : Elsevier. - 0165-6147 .- 1873-3735. ; 40:6, s. 403-418
-
Forskningsöversikt (refereegranskat)abstract
- Metastasis is a major cause of cancer-related mortality, accounting for 90% of cancer deaths. The explosive growth of cancer biology research has revealed new mechanistic network information and pathways that promote metastasis. Consequently, a large number of antitumor agents have been developed and tested for their antimetastatic efficacy. Despite their exciting cytotoxic effects on tumor cells in vitro and antitumor activities in preclinical studies in vivo, only a few have shown potent antimetastatic activities in clinical trials. In this review, we provide a brief overview of current antimetastatic strategies that show clinical efficacy and review nanotechnology-based approaches that are currently being incorporated into these therapies to mitigate challenges associated with treating cancer metastasis.
|
|
| 7. |
- Blennow, Kaj, 1958, et al.
(författare)
-
Amyloid biomarkers in Alzheimer's disease.
- 2015
-
Ingår i: Trends in pharmacological sciences. - : Elsevier BV. - 1873-3735 .- 0165-6147. ; 36:5, s. 297-309
-
Tidskriftsartikel (refereegranskat)abstract
- Aggregation of amyloid-β (Aβ) into oligomers, fibrils, and plaques is central in the molecular pathogenesis of Alzheimer's disease (AD), and is the main focus of AD drug development. Biomarkers to monitor Aβ metabolism and aggregation directly in patients are important for further detailed study of the involvement of Aβ in disease pathogenesis and to monitor the biochemical effect of drugs targeting Aβ in clinical trials. Furthermore, if anti-Aβ disease-modifying drugs prove to be effective clinically, amyloid biomarkers will be of special value in the clinic to identify patients with brain amyloid deposition at risk for progression to AD dementia, to enable initiation of treatment before neurodegeneration is too severe, and to monitor drug effects on Aβ metabolism or pathology to guide dosage. Two types of amyloid biomarker have been developed: Aβ-binding ligands for use in positron emission tomography (PET) and assays to measure Aβ42 in cerebrospinal fluid (CSF). In this review, we present the rationales behind these biomarkers and compare their ability to measure Aβ plaque load in the brain. We also review possible shortcomings and the need of standardization of both biomarkers, as well as their implementation in the clinic.
|
|
| 8. |
|
|
| 9. |
- Epstein, David H., et al.
(författare)
-
Science-Based Actions Can Help Address the Opioid Crisis
- 2018
-
Ingår i: TIPS - Trends in Pharmacological Sciences. - : ELSEVIER SCIENCE LONDON. - 0165-6147 .- 1873-3735. ; 39:11, s. 911-916
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The epidemic of addiction and over-dose is real. Addiction among pain patients accounts for only a small proportion but a large number. Scientific opinion leaders can be most effective on two fronts, each relatively low-tech: dissemination and oversight of empirically established treatments, and promulgation of social-science-based strategies for population-level prevention.
|
|
| 10. |
- Evers, Bastiaan, et al.
(författare)
-
Targeting homologous recombination repair defects in cancer
- 2010
-
Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 31:8, s. 372-380
-
Forskningsöversikt (refereegranskat)abstract
- DNA repair is essential for cells to maintain genome stability in an environment that constantly produces DNA damage. There is a growing appreciation that defects in homologous recombination repair underlie hereditary and sporadic tumourigenesis, and that deficiency in this pathway may dictate the sensitivity of tumours to certain DNA-damaging agents. Homologous recombination deficiency (HRD) may therefore prove to be a diagnostic criterion per se if appropriate biomarkers become available to identify these tumours. In addition, homologous recombination-deficient tumours are more sensitive to inhibition of other DNA repair pathways through so-called 'synthetic lethal interactions', a principle that is currently being tested in clinical trials. Finally, homologous recombination repair-deficient cells may have an increased dependency on certain cell-cycle checkpoints, which can be therapeutically exploited. Here we describe recent advances in strategies to identify and target HRD tumours, approaches to overcome resistance, and combinatory strategies to optimize treatment outcome.
|
|
