biostudies-literatureUnknown71Huang YCisplatin-based chemotherapy causes hearing loss in 40-60 % of all patients, yet effective preventative options remain limited. Building on prior animal studies, we demonstrate that oral administration of AZD5438, a potent and selective CDK2 inhibitor, provides dose-dependent protection against hearing loss in a clinically relevant multi-dose cisplatin mouse model. Protective doses (4.7 and 9.4 mg/kg b.i.d.) fall within the human-equivalent maximum tolerated dose range established in AstraZeneca trials, and exhibit plasma pharmacokinetics comparable to those in humans. Importantly, AZD5438 at 9.4 mg/kg b.i.d. does not reduce cisplatin's anti-tumor efficacy in a testicular cancer xenograft model, consistent with in vitro findings. These results support AZD5438 as a promising candidate for cNeoplasia (New York, N.Y.)101250https://www.ebi.ac.uk/biostudies/studies/S-EPMC12634867biostudies-literatureOral AZD5438 is a clinically translatable otoprotectant against cisplatin-induced hearing loss.PMC12634867Vesanes ETeitz THuang YZuo JZhang XfalseOral AZD5438 is a clinically translatable otoprotectant against cisplatin-induced hearing loss.Cisplatin-based chemotherapy causes hearing loss in 40-60 % of all patients, yet effective preventative options remain limited. Building on prior animal studies, we demonstrate that oral administration of AZD5438, a potent and selective CDK2 inhibitor, provides dose-dependent protection against hearing loss in a clinically relevant multi-dose cisplatin mouse model. Protective doses (4.7 and 9.4 mg/kg b.i.d.) fall within the human-equivalent maximum tolerated dose range established in AstraZeneca trials, and exhibit plasma pharmacokinetics comparable to those in humans. Importantly, AZD5438 at 9.4 mg/kg b.i.d. does not reduce cisplatin's anti-tumor efficacy in a testicular cancer xenograft model, consistent with in vitro findings. These results support AZD5438 as a promising candidate for c2025-01-01T00:00:00Z2025 Nov2026-06-05T17:46:48.048Z2026-05-19T03:11:50.182ZS-EPMC126348674118766310.1016/j.neo.2025.101250