Histone deacetylase 1, Histone deacetylase 2, Histone deacetylase 3, Histone deacetylase 8, and Lanosterol 14-alpha demethylase (HDAC1/2/3/8 + CYP51)

The target combination of Histone Deacetylases 1, 2, 3, and 8 (HDAC1/2/3/8) and Lanosterol 14-alpha demethylase (CYP51) represents a multi-target therapeutic strategy primarily explored in oncology and infectious diseases. HDAC1, 2, 3, and 8 are Class I enzymes responsible for removing acetyl groups from lysine residues on histones, thereby regulating chromatin structure and gene transcription related to cell survival and proliferation (UniProt P19367, Q92769). CYP51 is a critical enzyme in the sterol biosynthesis pathway, converting lanosterol to 14-demethyl lanosterol, which is essential for maintaining cell membrane integrity in fungi and parasites, as well as cholesterol production in humans (UniProt Q16850). Dual inhibition of these targets aims to achieve synergistic effects by simultaneously disrupting epigenetic maintenance and metabolic pathways. In cancer, this approach can lead to cell cycle arrest and apoptosis, while in parasitic infections like Chagas disease, it impairs both the parasite's gene regulation and its ability to form functional membranes (PubMed 32441545). This multi-target profile is often addressed using hybrid molecules that combine a zinc-binding group for HDAC inhibition with an azole moiety for CYP51 binding (PubMed 31002256).

Other names

Class I Histone Deacetylases and Sterol 14-alpha demethylaseHDAC1/2/3/8 and CYP51A1HDAC1-3, 8 and CYP51Dual HDAC and CYP51 target

Simultaneous inhibition of Class I histone deacetylases (HDAC1, 2, 3, and 8) to increase histone acetylation and alter gene expression, combined with the inhibition of lanosterol 14-alpha demethylase (CYP51) to disrupt sterol/cholesterol biosynthesis.