2022 completes the first complete year of open-access (OA) publishing for SLAS Discovery. The change to OA has been well-received by the scientific community, allowing for more immediate and free access and sharing of cutting-edge science. We continue to publish intriguing and provocative research in the form of Reviews, Perspectives, Original Research Articles and Technical Briefs. In 2022, we also added a “Protocols” manuscript type to enable the publication of detailed methods. The goal of SLAS Discovery is, and continues to be, to inform, share, educate, and encourage collaboration.
Once again, we are pleased to announce the Editor's Top 10 articles. For 2022, these articles primarily focused on common and topical interests: COVID-19 [
1
, 2
, 3
], 3D/organoid systems [4
, 5
, 6
, 7
, 8
], and diseases with great unmet medical need, such as autism [- Mediouni S.
- Mou H.
- Otsuka Y.
- Jablonski J.A.
- Adcock R.S.
- Batra L.
- Chung D.-H.
- Rood C.
- de Vera I.M.S.
- Rahaim R.
- Jr Ullah S.
- Yu X.
- Getmanenko Y.A.
- Kennedy N.M.
- Wang C.
- Nguyen T.-T.
- Hull M.
- Chen E.
- Bannister T.D.
- Baillargeon P.
- Scampavia L.
- Farzan M.
- Valente S.T.
- Spicer T.P.
Identification of potent small molecule inhibitors of SARS-CoV-2 entry.
[9]
] and obesity [[7]
,[10]
].COVID-19, or SARS-CoV-2, continues to plague the world as it adapts and mutates. On the positive side, the scientific community has rallied to produce a variety of effective treatments to reduce mortality and severity of disease. However, there remains great unmet medical and the concomitant desire for more effective and/or preventative treatments. The search continues for new molecules which can circumvent the disease. Ge et al., have utilized DNA-encoded libraries to identify novel covalent inhibitors of the protease [
[1]
]. The laboratories of Xu and Mediouni have each taken approaches of high throughput screening for small molecule inhibitors of SARS-CoV-2 entry [[2]
,[3]
]. It is hoped that these screening efforts will spawn full drug discovery programs to bring small molecule inhibitors of SARS-CoV-2 to clinic.The Top 10 articles also reflect the continuing desire to find more physiologically relevant and “clinically translatable” model system to better reflect the diseased patient tissue(s). The increased development, characterization and use of 3D culture, organoids and tumoroid systems is indicative of that need [
4
, 5
, 6
, 7
, 8
]. These 2022 articles have already been highly cited and downloaded in their first year of publication. It is notable that Close and Johnston [- Mediouni S.
- Mou H.
- Otsuka Y.
- Jablonski J.A.
- Adcock R.S.
- Batra L.
- Chung D.-H.
- Rood C.
- de Vera I.M.S.
- Rahaim R.
- Jr Ullah S.
- Yu X.
- Getmanenko Y.A.
- Kennedy N.M.
- Wang C.
- Nguyen T.-T.
- Hull M.
- Chen E.
- Bannister T.D.
- Baillargeon P.
- Scampavia L.
- Farzan M.
- Valente S.T.
- Spicer T.P.
Identification of potent small molecule inhibitors of SARS-CoV-2 entry.
[4]
] have developed methods for detecting hypoxic regions in head and neck tumor spheroids; perhaps implicating a method which could be used to identify potential modulators of hypoxia in the tumors.Pancreatic cancer remains a challenging tumor to treat, generally progressing quickly with poor prognosis. In part, it is thought that better pre-clinical models are needed to ensure clinical translation in drug discovery. Fernandez-Vega and colleagues [
[5]
] have led the efforts by completing the first 150k compound screen utilizing primary patient organoids and cross-correlated the results with autologous patient fibroblasts, i.e., normal cells. Similarly, Triple-Negative Breast Cancer (TNBC) is also a cancer with great unmet medical need. Cromwell et al. [[6]
] reported a novel method for processing and multi-functional profiling of breast tumoroid samples using a novel flow chip system in combination with high content imaging and metabolite analysis. As such, these methods for multi-parametric profiling of drug effects in patient-derived tumoroids could provide an in depth understanding of drug sensitivity in TNBC, and perhaps other tumor types, with important implications for the future development of personalized medicine.Avelino et al., [
[7]
] describes an approach using mass-spectrometry based proteomics to better characterize 3T3L1 adipocyte spheroids and compare with murine white adipose tissue (WAT). These investigators confirmed that the in vitro 3D culture of differentiated 3T3L1 adipocytes shared important molecular pathways with the WAT, including expression of proteins involved in central metabolic process of the adipose tissue.There is also the need to for better models of Dry Eye Disease, as described by Rodboon and coworkers [
[8]
]. Dysfunction and damage of the lacrimal gland results in ocular discomfort and Dry Eye Disease. Current therapies for Dry Eye Disease do not fully supply adequate lubrication to support optimal vision. Rodboon et al. has developed a novel magnetic three-dimensional (3D) bioprinting (M3DB) system for the 3D in vitro biofabrication of cellularized tissues, such as lacrimal gland organoids, using magnetic nanoparticles to bring cells together. This system holds promise to be a functional model of lacrimal gland tearing, platform for drug screening, and may offer clinical applications for Dry Eye Disease.- Mediouni S.
- Mou H.
- Otsuka Y.
- Jablonski J.A.
- Adcock R.S.
- Batra L.
- Chung D.-H.
- Rood C.
- de Vera I.M.S.
- Rahaim R.
- Jr Ullah S.
- Yu X.
- Getmanenko Y.A.
- Kennedy N.M.
- Wang C.
- Nguyen T.-T.
- Hull M.
- Chen E.
- Bannister T.D.
- Baillargeon P.
- Scampavia L.
- Farzan M.
- Valente S.T.
- Spicer T.P.
Identification of potent small molecule inhibitors of SARS-CoV-2 entry.
Autism Spectrum Disorder (ASD) is a heterogeneous developmental disorder that affects millions worldwide, and yet has no known definitive treatment/cure. Rao et al. [
[9]
] have endeavored to identify potential treatments for ASD by screening iPSC, including those from individuals with candidate driver mutations, for effects on neurite outgrowth. This report includes all methods, phenotypic outcomes, and results for the largest ASD small molecule screening effort done to date.As mentioned, it is the goal of SLAS Discovery to share and educate. In the form of Perspective and Review articles, authors are able to collate the state-of-the-art in the context of previous history, and comment on best practices. In the last of our Top 10 articles, Tsui [
[10]
] provides a Perspective and extremely useful summary on the utilization of adipocytes for high throughput screening and anti-obesity drug discovery.To conclude, we have highlighted the Top 10 articles for 2022 but there are certainly many more which we believe will be highly read, cited, and downloaded. I thank all of the authors, editors, and reviewers for their efforts in bringing such excellent content to SLAS Discovery and our readers. I look forward to all of the exciting science coming forward in 2023!
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
- Discovery of SARS-CoV-2 main protease covalent inhibitors from a DNA-encoded library selection.SLAS Discovery. 2022; 27: 79-85https://doi.org/10.1016/j.slasd.2022.01.001
- Detection and impact of hypoxic regions in multicellular tumor spheroid cultures formed by head and neck squamous cell carcinoma cells lines.SLAS Discovery. 2022; 27: 39-54https://doi.org/10.1016/j.slasd.2021.10.008
- Lead identification using 3D models of pancreatic cancer.SLAS Discovery. 2022; 27: 159-166https://doi.org/10.1016/j.slasd.2022.03.002
- Mass spectrometry-based proteomics of 3D cell culture: A useful tool to validate culture of spheroids and organoids.SLAS Discovery. 2022; 27: 167-174https://doi.org/10.1016/j.slasd.2021.10.013
- Development of high-throughput lacrimal gland organoid platforms for drug discovery in dry eye disease.SLAS Discovery. 2022; 27: 151-158https://doi.org/10.1016/j.slasd.2021.11.002
- Multifunctional profiling of triple-negative breast cancer patient-derived tumoroids for disease modeling.SLAS Discovery. 2022; 27: 191-200https://doi.org/10.1016/j.slasd.2022.01.006
- A high throughput screening assay for inhibitors of SARS-CoV-2 pseudotyped particle entry.SLAS Discovery. 2022; 27: 86-94https://doi.org/10.1016/j.slasd.2021.12.005
- Identification of potent small molecule inhibitors of SARS-CoV-2 entry.SLAS Discovery. 2022; 27: 8-19https://doi.org/10.1016/j.slasd.2021.10.012
- Screening for modulators of autism spectrum disorder using induced human neurons.SLAS Discovery. 2022; 27: 128-139https://doi.org/10.1016/j.slasd.2022.01.004
- Adipocyte-based high throughput screening for anti-obesity drug discovery: Current status and future perspectives.SLAS Discovery. 2022; 27: 375-383https://doi.org/10.1016/j.slasd.2022.08.001
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Published online: January 10, 2023
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