Zolinza (vorinostat)

Drug sensitivity analysis demonstrated that high TYMS expression positively correlated with sensitivity to Afatinib and Gefitinib, but negatively correlated with Methotrexate and Vorinostat. In conclusion, TYMS is upregulated in LUAD and may serve as an independent prognostic biomarker and therapeutic target.

P1, N=20, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2027

P1, N=30, Recruiting, New York Medical College | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2026

Although pancreatic ductal adenocarcinoma (PDAC) is generally considered an immunologically "cold" tumor, approximately 20% of cases can be classified as immune-hot. Single-cell RNA sequencing revealed that the Gemcitabine-SAHA combination remodels the tumor microenvironment by enhancing CD8+ T cell function and depleting cancer-associated fibroblasts. Clinically, we defined a CD8high/FASNhigh/PARP9high signature that identifies an IE patient subgroup with poor survival, representing those most likely to benefit from the "Gemcitabine-Nivolumab-SAHA" triple-combination therapy.

This study aimed to investigate the regulatory effect of suberoylanilide hydroxamic acid (SAHA) on HLA-E expression via the PERK/ATF4/CHOP pathway in NB...Moreover, SAHA inhibited the expression of ERS pathway proteins, including PERK and CHOP, in NB cell lines. This study demonstrated that SAHA downregulates HLA-E expression by inhibiting the PERK/ATF4/CHOP pathway, offering new insights into the regulation of tumor proliferation, migration, and immune evasion in NB.

Taken together, these results indicated that SAHA inhibition of FOXM1 oncogenic signaling may be mediated by MYCN in RB. Although the current data provide a preclinical rationale for the consideration of SAHA either as a single agent or in combination with other therapies, for the treatment of metastatic RB with MYCN-amplified RB1-/RB1-molecular phenotype, further research is warranted to gain greater insight into FOXM1-MYCN interaction in response to SAHA, in this molecular subtype of RB.

This study establishes FLG as a novel therapeutic target in GBM and validates the suppressive efficacy of cp8 on the characteristics of TMZ resistance, highlighting the translational potential as a multitargeted therapy against TMZ-resistant GBM.

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.