Histone deacetylase 1, 2, 3, and 10 and DNA topoisomerase II (HDAC1/2/3/10 + TOP2)

The target HDAC1/2/3/10 + DNA topoisomerase II refers to a multi-target therapeutic approach that simultaneously inhibits specific histone deacetylases (HDACs) and DNA topoisomerase II (Top2). HDACs 1, 2, and 3 (Class I) and HDAC10 (Class IIb) are enzymes responsible for removing acetyl groups from histones, which results in a condensed chromatin structure and the silencing of tumor suppressor genes (UniProt P19367, Q92769, O15379, Q969S8). DNA topoisomerase II (alpha and beta isoforms) is essential for managing DNA supercoiling during replication and transcription by creating transient double-strand breaks (UniProt P11388, P19012). The rationale for this dual-targeting strategy is based on the synergy where HDAC inhibition relaxes the chromatin, making the DNA more susceptible to Top2-mediated damage, thereby increasing the frequency of double-strand breaks and triggering apoptosis (PubMed: 28841315). This approach is primarily investigated in oncology to overcome resistance to conventional chemotherapy in hematological malignancies and solid tumors. Experimental dual inhibitors like DMP-001 are being developed to hit these targets concurrently, aiming for higher efficacy and lower resistance compared to single-agent therapies.

Other names

Class I and IIb HDACs and Topoisomerase IIHDAC/Top2 dual targetHDAC1/2/3/10 and TOP2A/B

Dual inhibition of histone deacetylases and DNA topoisomerase II, resulting in chromatin relaxation, increased DNA double-strand breaks, and induction of apoptosis.