Zolinza (vorinostat)

P1/2, N=25, Completed, Hackensack Meridian Health | Phase classification: P2b --> P1/2

P1, N=18, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

The new candidates showed considerable in vitro activity against MDA-MB-231 and HCT-116 cancer cell lines, in particular 4-hydroxyphenylbenzamide derivative of 3-ethylquinazolinone 7d, which revealed IC50 of 5.39 ± 0.08 μM and 4.11 ± 0.13 μM, in comparison with IC50 of 29.13 ± 2.28 μM and 33.50 ± 2.43 μM, obtained for the reference drug, sorafenib, respectively...Whereas, It was approximately 1.26 times more potent than vorinostat against HDAC-2, demonstrating an IC50 of 0.363 ± 0.013 μM...Meanwhile, the expression level of caspase-3 and the BAX/BCL-2 ratio were markedly elevated in HCT-116 cells treated with 7d. Finally, the presented data are reliable for developing dual VEGFR-2 and HDAC inhibitors as anticancer drugs and reveal lead molecules for such purpose.

Moreover, ADMET prediction tools indicated that compounds 7a and 9b may have more favorable pharmacokinetic properties than the gold-standard HDAC inhibitor, SAHA. Further study and exploration of the derivatives of compounds 7a and 9a can lead to further advancement in the development of potent HDAC inhibitor anticancer drugs.

Vorinostat exhibited the highest binding affinity to TPX2 (-29.32 kcal/mol) and BUB1B (-23.71 kcal/mol), followed by BRD-K90370028 (-18.40 kcal/mol on BUB1B), NSC19630 and Dasatinib (with consistent dual-target binding), CD-437, and four additional prioritised compounds that exhibited favourable interactions. In conclusion, this coherent transcriptomics-to-therapeutics workflow establishes TPX2 and BUB1B as strong prognostic biomarkers in BC, with promising repurposed drugs targeting these mitotic regulators.

Leveraging scaffold hopping and structural optimization strategies, we developed fifteen indole-based derivatives utilizing vorinostat (SAHA) and entinostat as lead compounds. Mechanistic investigations of representative hydroxamate and benzamide derivatives corroborated their marked antiproliferative effects in HCT-116 cancer cells and manifested a favorable safety profile against the normal fibroblasts (WI-38). Altogether, these findings underscore the therapeutic potential of the identified potent compounds for combating cancer via HDAC1/6 inhibition.

The HDAC8 PROTAC demonstrated stronger antitumor activity than HDAC8i and pan-HDACi vorinostat...HDAC8 PROTAC selectively suppressed glioblastoma cell growth and viability by arresting the cell cycle and inducing ER stress-mediated apoptosis via the IRE1α/XBP1s-JNK-CHOP pathway. Hence, HDAC8 PROTAC is a potential therapeutic agent for glioblastoma treatment.

Based on in vivo experiments in mice, our research highlights that the administration of specific agents-AZD3759 for HER2+, Vorinostat for TNBC, and SGC0946 for Luminal-when combined with anti-PD-1 therapy, not only boosts therapeutic effectiveness but also transforms the immunological environment within tumors. This synergistic approach led to notable reductions in tumor volume and an increase in cytotoxic T cell density in in vivo and in vitro experiments, further validating the role of AMrs scores in tailoring treatment modalities across BRCA subtypes. Overall, our study elucidates the critical role of APOBEC family genes in BRCA heterogeneity, highlighting their potential as biomarkers for personalized therapeutic approaches and pointing towards future research directions in integrating APOBEC-related mechanisms with immunotherapy.

We developed a reusable multimodal diagnostic framework with candidate biomarkers and a radiomics tool to facilitate the early detection and risk stratification of HCC.

P1, N=28, Active, not recruiting, The Methodist Hospital Research Institute | Trial completion date: Mar 2026 --> Dec 2026

Our findings suggest that the UMG1/CD3ε-BTCE selectively exerts potent anti-tumor activity against a relevant subset of TCLs. These findings support the development of a precision immunotherapy approach for patients with UMG1-expressing aggressive hematologic malignancies.

Commonly used GSIs include DAPT and RO4929097, which enhance the efficacy of agents, such as gemcitabine (PDAC), paclitaxel, osimertinib, erlotinib, and crizotinib (NSCLC), and 5-FU (gastric cancer, TNBC)...Additional research directions include addressing the tumor microenvironment and EMT-driven resistance, elucidating the mechanisms of immune evasion, and inhibiting tumor angiogenesis. Finally, leveraging artificial intelligence and big-data-driven personalized medicine, including sex-specific considerations, will be essential for improving patient outcomes.