Hexadodecane derivative compounds designed as HDAC11 inhibitors

Overview

This research presents a series of novel hexadodecane derivatives designed to act as selective inhibitors of histone deacetylase 11 (HDAC11), an epigenetic enzyme implicated in a range of disease pathways. The compounds are built upon the structural foundation of SIS17, a known HDAC11-selective inhibitor, with the key innovation being the replacement of the hydrazine moiety. This modification aims to improve the pharmacological profile of the molecules, potentially enhancing selectivity, reducing toxicity, and improving metabolic stability compared to the parent compound.

HDAC11 is the least understood member of the HDAC family and represents an emerging target in drug discovery. Selective inhibition of HDAC11 is of interest in oncology (particularly in hematological cancers), immunology (immune cell regulation and inflammation), and metabolic disorders. By providing new chemical scaffolds with improved properties, this research addresses a critical gap in the availability of high-quality chemical probes and lead compounds for HDAC11-targeted drug development.

Technical specifications

• Core innovation: Novel hexadodecane-based scaffold derived from the structure of SIS17, a validated HDAC11-selective inhibitor
• Structural modification: Replacement of the hydrazine moiety to improve the inhibitor's selectivity and safety profile
• Mechanism of action: Selective enzymatic inhibition of HDAC11, enabling targeted epigenetic modulation
• Compound class: Small-molecule organic derivatives suitable for medicinal chemistry optimization and structure-activity relationship studies
• Applications: Useful as chemical probes for HDAC11 biology, lead compounds for drug discovery, and starting points for further medicinal chemistry campaigns

Technology readiness level

The compounds are at an early-stage research and design phase. The research hypothesis is based on rational drug design principles applied to a validated HDAC11-selective scaffold (SIS17). Further experimental validation is required, including enzymatic inhibition assays, selectivity profiling against other HDAC isoforms, cell-based activity testing, and preliminary pharmacokinetic evaluation to confirm the advantages of the hydrazine replacement strategy. The project is positioned for early-stage collaboration with industry partners interested in HDAC11 drug discovery, epigenetic therapeutics, or novel chemical probe development.