Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321 College Avenue, CCR r.605, Fort Lauderdale, FL 33314, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA.
Biomolecules. 2023 Feb 10;13(2):349. doi: 10.3390/biom13020349.
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.
尽管黑色素瘤治疗在最近取得了进展，但仍迫切需要新的靶点和新的治疗方法。我们之前曾报道过通过结合和下调剪接体蛋白 hnRNPH1 和 H2 起作用的黑色素瘤激活剂。鉴于我们对在人类中使用剪接体结合物的副作用知之甚少，因此进行了一项急性毒性研究，以评估这些化合物在小鼠中的作用。雄性和雌性小鼠通过皮下注射以 50mg/kg/天的剂量接受化合物 2155-14 和 2155-18 的治疗，监测 21 天的痛苦迹象，并与对照小鼠进行比较。此外，还评估了这些先导化合物对血液化学、血细胞计数和器官的影响。在化合物处理后，小鼠的体重、血细胞计数、血液化学或器官均未发生明显变化。结果表明，在三周的研究期间，我们的化合物 2155-14 和 2155-18 对小鼠没有毒性。
