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In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2
Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. Given the lack of knowledge about the side effects of using spli...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953269/ https://www.ncbi.nlm.nih.gov/pubmed/36830718 http://dx.doi.org/10.3390/biom13020349 |
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author | Velayutham, Sadeeshkumar Seal, Trisha Danthurthy, Samaya Zaias, Julia Smalley, Keiran S. M. Minond, Dmitriy |
author_facet | Velayutham, Sadeeshkumar Seal, Trisha Danthurthy, Samaya Zaias, Julia Smalley, Keiran S. M. Minond, Dmitriy |
author_sort | Velayutham, Sadeeshkumar |
collection | PubMed |
description | Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. Given the lack of knowledge about the side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50 mg/kg/day via subcutaneous injections, and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, the effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the body weight, blood cell count, blood chemistry, or organs of the mice following the compound treatment. The results show that our compounds, 2155-14 and 2155-18, are not toxic for the study period of three weeks. |
format | Online Article Text |
id | pubmed-9953269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99532692023-02-25 In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2 Velayutham, Sadeeshkumar Seal, Trisha Danthurthy, Samaya Zaias, Julia Smalley, Keiran S. M. Minond, Dmitriy Biomolecules Brief Report Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. Given the lack of knowledge about the side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50 mg/kg/day via subcutaneous injections, and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, the effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the body weight, blood cell count, blood chemistry, or organs of the mice following the compound treatment. The results show that our compounds, 2155-14 and 2155-18, are not toxic for the study period of three weeks. MDPI 2023-02-10 /pmc/articles/PMC9953269/ /pubmed/36830718 http://dx.doi.org/10.3390/biom13020349 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Velayutham, Sadeeshkumar Seal, Trisha Danthurthy, Samaya Zaias, Julia Smalley, Keiran S. M. Minond, Dmitriy In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2 |
title | In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2 |
title_full | In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2 |
title_fullStr | In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2 |
title_full_unstemmed | In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2 |
title_short | In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2 |
title_sort | in vivo acute toxicity studies of novel anti-melanoma compounds downregulators of hnrnph1/h2 |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953269/ https://www.ncbi.nlm.nih.gov/pubmed/36830718 http://dx.doi.org/10.3390/biom13020349 |
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