Preprint Brief Report Version 1 Preserved in Portico This version is not peer-reviewed

In vivo Acute Toxicity Studies of Novel Melanoma Actives

Version 1 : Received: 28 October 2022 / Approved: 3 November 2022 / Online: 3 November 2022 (01:43:05 CET)

A peer-reviewed article of this Preprint also exists.

Velayutham, S.; Seal, T.; Danthurthy, S.; Zaias, J.; Smalley, K.S.M.; Minond, D. In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2. Biomolecules 2023, 13, 349. Velayutham, S.; Seal, T.; Danthurthy, S.; Zaias, J.; Smalley, K.S.M.; Minond, D. In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1/H2. Biomolecules 2023, 13, 349.

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 (Palrasu et al., 2019). Given lack of knowledge about 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 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs 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.

Keywords

melanoma; drug discovery; spliceosomal inhibition; acute toxicity; blood chemistry; organ histopathology

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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