Drug Discovery

Technology Networks

In this episode, we will be speaking with *Paul Andrews, Director of Operations at the National Phenotypic Screening Centre, who will be talking to us about drug screening strategies and preclinical drug development. This series is kindly brought to you by CN Bio, click here to find out more: https://bit.ly/2xFrpC1 *(speaker and sponsor are not affiliated)

TSE Explores Drug Discovery - Testing a Drug Compound: Preclinical Screening S05E03

Analytical Cannabis 

Speaking at the Analytical Cannabis Expo Europe Online 2022, Tej Virk delivered his talk on market expectations for the European Medical Industry.

Market Expectation for the European Medical Industry

XenoTech

Presenter:  Chris Bohl, Ph.D., Global Technical Support Manager

This ADME 101 video provides an overview of different types of subcellular fractions, such as microsomes, S9, cytosol, lysosomes and homogenate, and their unique benefits for use in various types of in vitro ADMET/DMPK & Drug-Drug Interaction studies. This short, information-packed webinar features:

The different types of subcellular fractions
How they are made
Who uses them, for which studies, and why
Advantages of the test systems
Different preparation options
Whether to use a NADPH regenerating system or 1mM NADPH
How tissue is procured and more...

Download slides: https://www.xenotech.com/webinar-slides/sekisui-xenotech-guide-to-subcellular-fractions.pdf
Questions, comments and requests: https://www.xenotech.com/contact-us 
More information on our research services and test systems: https://www.xenotech.com
Other previously aired webinars: https://www.xenotech.com/scientific-resources/webinar-series
Upcoming webinar notifications: https://www.xenotech.com/newsletter-signup
Request a webinar topic: https://www.xenotech.com/scientific-resources/upcoming-webinars

About the presenter: Dr. Chris Bohl received his PhD from the School of Biological Sciences from the University of Nebraska – Lincoln and has been with XenoTech since 2014, first operating as a research scientist before becoming the Senior Manager of Technical Support for Products.

ADME 101 Guide to Subcellular Fractions and When to Use Which Test System

Oncotarget

Oncotarget published this trending research paper in Volume 14, entitled, “Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels" by the researchers from Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig 04103, Germany; Institute of Pathology, Medical Faculty, University of Leipzig, Leipzig 04103, Germany; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, and German Cancer Consortium (DKTK) partner site Essen/Düsseldorf, Essen 45122, Germany.

DOI - https://doi.org/10.18632/oncotarget.28342

Correspondence to - Christina Kuhn - Christina.Kuhn@medizin.uni-leipzig.de 

Abstract

Overexpression of the dihydrolipoamide S-succinyltransferase (DLST) is associated with poor outcome in neuroblastoma patients and triple-negative breast cancer (TNBC) and specifically with the oxidative phosphorylation (OXPHOS) pathway. Inhibitors of OXPHOS were previously suggested as a potential therapeutic strategy for a subset of patients with high-risk neuroblastoma. Here, we tested if cell lines with DLST amplifications or high mRNA levels were associated with sensitivity to 250 drugs from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset by comparing them to cell lines without these changes. DLST-altered cell lines were more sensitive to 7 approved drugs, among these obatoclax mesylate, a BCL2 inhibitor that reduces OXPHOS in human leukemia stem cells. Moreover, several protein kinase inhibitors were identified to be efficient in cell lines with DLST amplifications or high mRNA levels, suggesting a vulnerability of DLST-altered cell lines for drugs targeting the ERK/MAPK pathway. Furthermore, increased DLST expression in cell lines with driver mutations in KRAS supported this relationship. We therefore conclude that, in addition to OXPHOS, protein kinases could be potential targets of therapy in the presence of DLST amplifications or high mRNA levels. The new drug candidates proposed here could serve in experimental testing on drug efficacy in knock-in cell lines and DLST-activated tumors.

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28342

Keywords - neuroblastoma, drug sensitivity, drug resistance, drug repurposing, DLST

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/OncotargetYouTube
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957

Drugs Associated With Sensitivity of Cancer Cell Lines With DLST or High mRNA Levels

Aging (Aging-US)

Aging-US published this research paper in Volume 15, Issue 1, entitled, "Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization" by researchers from the Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA; Department of Molecular Medicine, UF Scripps Biomedical Research, Jupiter, FL; BIO5 Institute and Department of Nutritional Sciences, University of Arizona, Tucson, AZ; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL.

DOI - https://doi.org/10.18632/aging.204480

Corresponding author - Jing Chen - jing.chen@childrens.harvard.edu 

Abstract

Choroidal neovascularization (CNV) causes acute vision loss in neovascular age-related macular degeneration (AMD). Genetic variations of the nuclear receptor RAR-related orphan receptor alpha (RORα) have been linked with neovascular AMD, yet its specific role in pathological CNV development is not entirely clear. In this study, we showed that Rora was highly expressed in the mouse choroid compared with the retina, and genetic loss of RORα in Staggerer mice (Rorasg/sg) led to increased expression levels of Vegfr2 and Tnfa in the choroid and retinal pigment epithelium (RPE) complex. In a mouse model of laser-induced CNV, RORα expression was highly increased in the choroidal/RPE complex post-laser, and loss of RORα in Rorasg/sg eyes significantly worsened CNV with increased lesion size and vascular leakage, associated with increased levels of VEGFR2 and TNFα proteins. Pharmacological inhibition of RORα also worsened CNV. In addition, both genetic deficiency and inhibition of RORα substantially increased vascular growth in isolated mouse choroidal explants ex vivo. RORα inhibition also promoted angiogenic function of human choroidal endothelial cell culture. Together, our results suggest that RORα negatively regulates pathological CNV development in part by modulating angiogenic response of the choroidal endothelium and inflammatory environment in the choroid/RPE complex.
Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204480

Keywords - age-related macular degeneration, angiogenesis, choroidal neovascularization, inflammation, nuclear receptors, RORα, VEGFR2, TNFα

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://youtube.com/Aging-US
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Genetic Deficiency and Pharmacological Modulation of RORα Regulate Laser-Induced CNV 

Oncotarget published this research paper in Volume 14, entitled, “Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001" by the researchers from the Research Development, Sutro Biopharma, South San Francisco, CA; Clinical Development, Sutro Biopharma, South San Francisco, CA.

DOI - https://doi.org/10.18632/oncotarget.28341

Correspondence to - Xiaofan Li - xli@sutrobio.com, and Arturo Molina - amolina@sutrobio.com

Abstract

Overexpression of CD74, a type II transmembrane glycoprotein involved in MHC class II antigen presentation, has been reported in many B-cell non-Hodgkin lymphomas (NHLs) and in multiple myeloma (MM). STRO-001 is a site-specific, predominantly single-species antibody-drug conjugate (ADC) that targets CD74 and has demonstrated efficacy in xenograft models of MM and tolerability in non-human primates. Here we report results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL. STRO-001 displayed nanomolar and sub-nanomolar cytotoxicity in 88% (15/17) of cancer cell lines tested. STRO-001 showed potent cytotoxicity on proliferating B cells while limited cytotoxicity was observed on naïve human B cells. A linear dose-response relationship was demonstrated in vivo for DLBCL models SU-DHL-6 and U2932. Tumor regression was induced at doses less than 5 mg/kg, while maximal activity with complete cures were observed starting at 10 mg/kg. In MCL Mino and Jeko-1 xenografts, STRO-001 starting at 3 mg/kg significantly prolonged survival or induced tumor regression, respectively, leading to tumor eradication in both models. In summary, high CD74 expression levels in tumors, nanomolar cellular potency, and significant anti-tumor in DLBCL and MCL xenograft models support the ongoing clinical study of STRO-001 in patients with B-cell NHL.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28341

Keywords - CD74, antibody-drug conjugate, non-Hodgkin lymphoma, xenograft models, STRO-001

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/OncotargetYouTube
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957

Targeting CD74 in B-cell Non-Hodgkin Lymphoma With Antibody-Drug Conjugate STRO-001

Speaking at ‘Advances in proteomics & Metabolomics’ 2022, Charlotte Stadler from SciLifeLab presented her talk on the generation of highly multiplexed immunofluorescence data and bridging the gap between research and conventional clinical pathology.

Generating Highly Multiplexed Immunofluorescence Data and Bridging the Gap Between Research and Conventional Clinical Pathology

Speaking at ‘Advances in Proteomics & Metabolomics’ 2022, Harrison Specht from Northeastern University presented his talk on accessible single cell proteomics by mass spectroscopy.

Accessible Single Cell Proteomics by Mass Spectrometry

Oncotarget published this trending research paper in Volume 13, entitled, “Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression" by the researchers from the Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC; Discovery Immunology, Merck Research Institute, Boston, MA; Discovery Oncology, Merck Research Institute, Boston, MA; Bicycle Therapeutics, Lexington, MA.

DOI - https://doi.org/10.18632/oncotarget.28330

Correspondence to - Robert I. Glazer - glazerr@georgetown.edu 

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28330

Keywords - PD-1, NeuT, Wnt, macrophages, mammary tumorigenesis, breast cancer

Abstract

One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors and remodeling of the extracellular matrix to produce an immune tolerant microenvironment. To determine whether tolerance is associated with the immune checkpoint, Programmed Cell Death 1 (PD-1), NeuT/ATTAC mice, a conditional model of mammary fibrosis that we recently developed, were administered a murine-specific anti-PD-1 mAb related to pembrolizumab, and drug response was monitored by tumor development, imaging mass cytometry, immunohistochemistry and tumor gene expression by RNAseq. Tumor progression in NeuT/ATTAC mice was unaffected by weekly injection of anti-PD-1 over four months. Insensitivity to anti-PD-1 was associated with several processes, including increased tumor-associated macrophages (TAM), epithelial to mesenchymal transition (EMT), fibroblast proliferation, an enhanced extracellular matrix and the Wnt signaling pathway, including increased expression of Fzd5, Wnt5a, Vimentin, Mmp3, Col2a1 and Tgfβ1. These results suggest potential therapeutic avenues that may enhance PD-1 immune checkpoint sensitivity, including the use of tumor microenvironment targeted agents and Wnt pathway inhibitors.

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/OncotargetYouTube
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957

Drug Discovery

Refine By

Keep up to date with all your favourite videos and channels.

Get personalised notifications on new releases and channel content by subscribing to the LabTube eNewsletter.