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Updated: Aug 9, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2
Sadeeshkumar Velayutham1,2, Trisha Seal3, Samaya Danthurthy4
1Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321 College Avenue, CCR r.605, Fort Lauderdale, FL 33314, USA.
Abstract:
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.
Insights
New melanoma treatments targeting spliceosomal proteins hnRNPH1 and H2 show no acute toxicity in mice. Compounds 2155-14 and 2155-18 were well-tolerated over a three-week study period.
Area of Science:
- Oncology
- Molecular Biology
- Toxicology
Background:
- Melanoma therapy urgently requires novel targets and treatment strategies.
- Previously identified melanoma-active compounds target and downregulate spliceosomal proteins hnRNPH1 and H2.
- Limited data exists on the human side effects of spliceosomal protein binders.
Purpose of the Study:
- To evaluate the acute toxicity of novel melanoma compounds 2155-14 and 2155-18.
- To assess potential adverse effects of spliceosomal binders in a preclinical model.
Main Methods:
- Male and female mice received subcutaneous injections of compounds 2155-14 and 2155-18 at 50 mg/kg/day.
- Clinical signs of distress were monitored for 21 days.
- Blood chemistry, complete blood counts, and organ evaluations were performed.
Main Results:
- No significant changes were observed in body weight, blood cell counts, or blood chemistry.
- No adverse effects were noted in the evaluated organs.
- Compounds 2155-14 and 2155-18 demonstrated no acute toxicity during the three-week study.
Conclusions:
- The novel melanoma compounds 2155-14 and 2155-18 are safe in mice over a three-week period.
- These findings support further investigation of these spliceosomal binders as potential melanoma therapeutics.
