ITOC2 – 024. Selective lysis of biphenotypic leukaemia cells is mediated by dual-targeting triplebody 33-3-19 treatment

2015 ◽  
Vol 51 ◽  
pp. S9
Author(s):  
Roskopf C. Claudia ◽  
Braciak A. Todd ◽  
Fenn Nadja ◽  
Kobold Sebastian ◽  
Jacob Uwe ◽  
...  
Keyword(s):  
Dual Targeting ◽  
Selective Lysis

scholarly journals Dual-targeting triplebody 33-3-19 mediates selective lysis of biphenotypic CD19+ CD33+ leukemia cells

Oncotarget ◽  
2016 ◽  
Vol 7 (16) ◽  
pp. 22579-22589 ◽  
Author(s):  
Claudia C. Roskopf ◽  
Todd A. Braciak ◽  
Nadja C. Fenn ◽  
Sebastian Kobold ◽  
Georg H. Fey ◽  
...  
Keyword(s):  
Leukemia Cells ◽  
Dual Targeting ◽  
Selective Lysis

Dual-targeting Janus Dendrimer Based Peptides for Bone Cancer: Synthesis and Preliminary Biological Evaluation

2013 ◽  
Vol 10 (8) ◽  
pp. 594-601 ◽  
Author(s):  
Bo Jiang ◽  
Jing Zhao ◽  
Yanhua Li ◽  
Dongsheng He ◽  
Junzhu Pan ◽  
...  
Keyword(s):  
Bone Cancer ◽  
Biological Evaluation ◽  
Dual Targeting

Multi-Targeting Anticancer Agents: Rational Approaches, Synthetic Routes and Structure Activity Relationship

2019 ◽  
Vol 19 (7) ◽  
pp. 842-874 ◽  
Author(s):  
Harbinder Singh ◽  
Nihar Kinarivala ◽  
Sahil Sharma
Keyword(s):  
Anticancer Agents ◽  
Cancer Drug ◽  
Design And Synthesis ◽  
Cancer Drug Discovery ◽  
Dual Targeting ◽  
Structure Activity ◽  
Anti Cancer ◽  
Dual Inhibitors ◽  
Recent Trends ◽  
Synthetic Routes

We live in a world with complex diseases such as cancer which cannot be cured with one-compound one-target based therapeutic paradigm. This could be due to the involvement of multiple pathogenic mechanisms. One-compound-various-targets stratagem has become a prevailing research topic in anti-cancer drug discovery. The simultaneous interruption of two or more targets has improved the therapeutic efficacy as compared to the specific targeted based therapy. In this review, six types of dual targeting agents along with some interesting strategies used for their design and synthesis are discussed. Their pharmacology with various types of the molecular interactions within their specific targets has also been described. This assemblage will reveal the recent trends and insights in front of the scientific community working in dual inhibitors and help them in designing the next generation of multi-targeted anti-cancer agents.

scholarly journals Genome communication in plants mediated by organelle–n­ucleus-located proteins

2020 ◽  
Vol 375 (1801) ◽  
pp. 20190397 ◽  
Author(s):  
Karin Krupinska ◽  
Nicolás E. Blanco ◽  
Svenja Oetke ◽  
Michela Zottini
Keyword(s):  
Chloroplast Development ◽  
Cell Cycle Control ◽  
Plastid Transformation ◽  
Light Responses ◽  
Dual Targeting ◽  
Dual Localization ◽  
Retrograde Signalling ◽  
Eukaryotic Proteins ◽  
Plastid Proteins ◽  
Associated Proteins

An increasing number of eukaryotic proteins have been shown to have a dual localization in the DNA-containing organelles, mitochondria and plastids, and/or the nucleus. Regulation of dual targeting and relocation of proteins from organelles to the nucleus offer the most direct means for communication between organelles as well as organelles and nucleus. Most of the mitochondrial proteins of animals have functions in DNA repair and gene expression by modelling of nucleoid architecture and/or chromatin. In plants, such proteins can affect replication and early development. Most plastid proteins with a confirmed or predicted second location in the nucleus are associated with the prokaryotic core RNA polymerase and are required for chloroplast development and light responses. Few plastid–nucleus-located proteins are involved in pathogen defence and cell cycle control. For three proteins, it has been clearly shown that they are first targeted to the organelle and then relocated to the nucleus, i.e. the nucleoid-associated proteins HEMERA and Whirly1 and the stroma-located defence protein NRIP1. Relocation to the nucleus can be experimentally demonstrated by plastid transformation leading to the synthesis of proteins with a tag that enables their detection in the nucleus or by fusions with fluoroproteins in different experimental set-ups. This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.

scholarly journals Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Yanfeng Dai ◽  
Xiang Yu ◽  
Jianshuang Wei ◽  
Fanxin Zeng ◽  
Yiran Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Scavenger Receptor ◽  
Intradermal Injection ◽  
Sentinel Lymph Nodes ◽  
Breast Cancer Surgery ◽  
Photoacoustic Microscopy ◽  
Dual Targeting ◽  
Scavenger Receptor Class ◽  
Distinct Distribution

Abstract Detection of sentinel lymph nodes (SLNs) is critical to guide the treatment of breast cancer. However, distinguishing metastatic SLNs from normal and inflamed lymph nodes (LNs) during surgical resection remains a challenge. Here, we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle (5K-HA-HPPS) loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer. The small sized (~40 nm) self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection. Compared with normal popliteal LNs (N-LN), there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs (T-MLN) and inflamed LNs (Inf-LN), respectively, 6 h after nanoparticle inoculation. More importantly, photoacoustic microscopy (PAM) of 5K-HA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN. Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN. The ratio of PA intensity (R) at the centre of the LNs compared with that at the periphery was 5.93 ± 0.75 for T-MLNs of the 5K-HA-HPPS group, which was much higher than that for the Inf-LNs (R = 0.2 ± 0.07) and N-LNs (R = 0.45 ± 0.09). These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs, thus guiding the removal of SLNs during breast cancer surgery.

scholarly journals Screening of 5- and 6-Substituted Amiloride Libraries Identifies Dual-uPA/NHE1 Active and Single Target-Selective Inhibitors

2021 ◽  
Vol 22 (6) ◽  
pp. 2999
Author(s):  
Benjamin J. Buckley ◽  
Ashna Kumar ◽  
Ashraf Aboelela ◽  
Richard S. Bujaroski ◽  
Xiuju Li ◽  
...  
Keyword(s):  
Selectivity Ratio ◽  
Dual Targeting ◽  
Sodium Hydrogen ◽  
Type Plasminogen Activator ◽  
Single Target ◽  
Urokinase Type Plasminogen Activator ◽  
Anti Cancer ◽  
Sodium Hydrogen Exchanger ◽  
A Cell ◽  
Cell Invasiveness

The K+-sparing diuretic amiloride shows off-target anti-cancer effects in multiple rodent models. These effects arise from the inhibition of two distinct cancer targets: the trypsin-like serine protease urokinase-type plasminogen activator (uPA), a cell-surface mediator of matrix degradation and tumor cell invasiveness, and the sodium-hydrogen exchanger isoform-1 (NHE1), a central regulator of transmembrane pH that supports carcinogenic progression. In this study, we co‑screened our library of 5- and 6-substituted amilorides against these two targets, aiming to identify single-target selective and dual-targeting inhibitors for use as complementary pharmacological probes. Closely related analogs substituted at the 6-position with pyrimidines were identified as dual-targeting (pyrimidine 24 uPA IC50 = 175 nM, NHE1 IC50 = 266 nM, uPA selectivity ratio = 1.5) and uPA-selective (methoxypyrimidine 26 uPA IC50 = 86 nM, NHE1 IC50 = 12,290 nM, uPA selectivity ratio = 143) inhibitors, while high NHE1 potency and selectivity was seen with 5-morpholino (29 NHE1 IC50 = 129 nM, uPA IC50 = 10,949 nM; NHE1 selectivity ratio = 85) and 5-(1,4-oxazepine) (30 NHE1 IC50 = 85 nM, uPA IC50 = 5,715 nM; NHE1 selectivity ratio = 67) analogs. Together, these amilorides comprise a new toolkit of chemotype-matched, non-cytotoxic probes for dissecting the pharmacological effects of selective uPA and NHE1 inhibition versus dual-uPA/NHE1 inhibition.

scholarly journals Dual targeting of cytokine storm and viral replication in COVID-19 by plant-derived steroidal pregnanes: an in silico perspective

2021 ◽  
pp. 104406
Author(s):  
Gideon A. Gyebi ◽  
Oludare M. Ogunyemi ◽  
Ibrahim M. Ibrahim ◽  
Saheed O. Afolabi ◽  
Joseph O. Adebayo
Keyword(s):  
Viral Replication ◽  
In Silico ◽  
Cytokine Storm ◽  
Dual Targeting
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