A Comprehensive In Vitro and In Silico Approach for Targeting 4-Hydroxyphenyl Pyruvate Dioxygenase: Towards New Therapeutics for Alkaptonuria.

ABSTRACT: Alkaptonuria (AKU) is an ultra-rare genetic disorder caused by mutations in the homogentisate 1,2-dioxygenase (HGD) gene, leading to the accumulation of homogentisic acid (HGA). Current treatment options are limited, with Nitisinone (Orfadin or NTBC) being the only approved drug. However, its long-term use raises concerns due to significant adverse effects, highlighting the urgent need for safer alternatives. AKU manifests with progressive and often painful symptoms, severely impacting patients' quality of life. Identifying new therapeutic approaches to inhibit 4-hydroxyphenyl pyruvate dioxygenase (4-HPPD) is critical to improving outcomes for AKU patients. In this study, we present a novel integrated in vitro and in silico strategy to assess the residence time of 4-HPPD inhibitors.

SUBMITTER: Bernardini G 

PROVIDER: S-EPMC11988800 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature