The Pharmacokinetics Evaluation of HDAC6-selective Inhibitors for Use in Therapeutic Strategies
Histone deacetylase 6 (HDAC6) is a protein known to be involved in a wide array of cancers. Although there are currently 4 approved HDAC inhibitors to date, these drugs lack the selectivity to only target HDAC6, given its high structural similarities with 10 other HDAC proteins, resulting in severe side-effects in patients such as nausea, diarrhea, and cardiac toxicities. Moreover, these approved drugs are also easily eliminated by the body, requiring the patients to take high doses frequently, further worsening the toxicity profile. To mitigate these drawbacks, we have developed >500 molecules with exceptional potency, HDAC6-selectivity, and stability. With promising efficacy in cancer cell models, the next aim of our research is to evaluate the stability of these compounds. We hope to use the pharmacokinetics profiles obtained to guide the development of stable, effective and safe molecules as the next generation of disease-modifying treatment for T-cells prolymphocytic leukaemia.