P1, N=19, Active, not recruiting, Massachusetts General Hospital | Trial primary completion date: Sep 2025 --> Sep 2026

Moreover, an extended drug screening analysis identified Cytarabine and Clofarabine as significantly synergizing with HDAC6 inhibitor (Ricolinostat) in myeloid leukemia cell lines and in patient-derived xenograft (PDX) cells, while showing limited synergy in lymphoid leukemia cell lines, PDX, or healthy control cells. These findings suggest that HDAC6 represents a promising therapeutic target in myeloid lineage-derived leukemia cells by simultaneously enhancing immune activation and increasing chemosensitivity.

P1/2, N=41, Recruiting, Novartis Pharma AG

Our findings indicate that SE-driven TCF4 can orchestrate metastatic transcriptional networks to maintain NB malignancy and propose ACY-1215 as a translational therapeutic candidate for clinical intervention.

P1, N=57, Completed, AnnJi Pharmaceutical Co., Ltd. | Recruiting --> Completed

This hypothesis was confirmed by SREBP-1 silencing, which also potentiated the antitumor efficacy of the ITF3756/BTZ combination in HCT116 cells. Overall, these results reveal a particular antitumor efficacy of the selective HDAC6 inhibitor in combination with BTZ in colon cancer cells and suggest that inhibiting lipogenesis is a useful tool to further increase the synergistic effectiveness.

10g also showed superior metabolic stability compared to ACY-1215 in a microsomal stability study. In summary, this work highlighted the therapeutic potential of aroylpyrrole-based sHDAC6 inhibitors and provided a valuable lead compound in treating cervical cancer.

P2, N=165, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P2, N=165, Not yet recruiting, Novartis Pharmaceuticals

The HDI-3 emerged as the most promising candidate among replicate simulations, exhibiting a substantially favorable MM/GBSA binding free energy of -130.67 kcal/mol-indicative of strong thermodynamic stability and stronger binding affinity compared to reference inhibitors Trichostatin A and Ricolinostat. Therefore, experimental validation is essential to confirm the compound's efficacy and safety. This integrated computational pipeline provides an efficient strategy to accelerate targeted drug discovery, laying the groundwork for future experimental investigations.

Furthermore, in an HCT116 xenograft mouse model, compound 5b significantly inhibited tumor growth without affecting body weight. The combination of in vitro and in vivo studies provides robust evidence supporting the potential of compound 5b as a highly potent and selective HDAC6 inhibitor, possessing promising anti-proliferative and apoptosis-inducing properties for further preclinical development.