Histone deacetylase 1 (HDAC1), Histone deacetylase 2 (HDAC2), Histone deacetylase 3 (HDAC3), Histone deacetylase 6 (HDAC6), and Beta-tubulin (HDAC1/2/3/6 + β-tubulin)

This multi-target profile consists of Histone Deacetylases (HDAC) 1, 2, 3, and 6, along with the structural protein Beta-tubulin. HDACs 1, 2, and 3 are Class I enzymes that regulate gene expression by removing acetyl groups from histones, while HDAC6 is a Class IIb enzyme that primarily functions in the cytoplasm to deacetylate non-histone proteins like alpha-tubulin (UniProt Q13547, Q92769, O15379, Q9UBN7). Beta-tubulin is a critical component of microtubules, essential for cell structure, intracellular transport, and mitotic spindle formation (UniProt P07437). Drugs targeting this combination, such as Citarinostat (ACY-241), aim to achieve synergistic anti-tumor effects by simultaneously disrupting epigenetic regulation, protein degradation pathways via the aggresome, and microtubule dynamics (NCI Drug Dictionary). This approach is particularly relevant in oncology, where it can overcome resistance to single-agent therapies and induce potent apoptosis in various malignancies, including multiple myeloma and solid tumors (PubMed 28842344). By inhibiting both the nuclear gene-regulatory functions of Class I HDACs and the cytoplasmic structural/degradative functions of HDAC6 and tubulin, these agents provide a comprehensive attack on cancer cell homeostasis.

Other names

HDAC/Tubulin dual targetHDAC1/2/3/6 and TubulinHistone deacetylase and microtubule protein complexHDAC and tubulin dual inhibitor target

Simultaneous inhibition of Class I and IIb histone deacetylases and disruption of microtubule dynamics through binding to the beta-tubulin subunit.