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Decades‑Old Drug Hydralazine Blocks Enzyme Linked to Aggressive Glioblastoma

Researchers at the University of Pennsylvania report that hydralazine inhibits the enzyme 2‑aminoethanethiol dioxygenase (ADO) in human and mouse cells. ADO helps aggressive glioblastoma tumors produce hypotaurine, which supports tumor survival and invasion; hydralazine blocked tumor growth in laboratory glioblastoma cells by silencing ADO. While results are encouraging, clinical trials are needed to confirm benefit in patients and to develop more selective ADO inhibitors.

02:52 PM, 11/28/2025Health
Decades‑Old Drug Hydralazine Blocks Enzyme Linked to Aggressive Glioblastoma

Hydralazine, a blood‑pressure medication used for decades, has been shown to inhibit a key enzyme that aggressive glioblastoma tumors exploit to survive and spread. Researchers at the University of Pennsylvania examined the drug's effects in human and mouse cells and identified 2‑aminoethanethiol dioxygenase (ADO) as a direct target.

ADO acts like an "alarm bell" for low oxygen in tissues. When activated, it triggers a cascade that degrades RGS proteins (regulators of G‑protein signaling), promoting blood‑vessel constriction and raising blood pressure. In glioblastoma, tumors often express high levels of ADO and hijack the enzyme to produce hypotaurine, a small molecule that helps cancer cells resist stress, survive longer, and invade surrounding tissue.

In laboratory experiments the team found hydralazine effectively silences ADO activity. With ADO suppressed, RGS proteins are preserved, vessels are less likely to constrict, and blood pressure falls. Importantly, in cultured human glioblastoma cells blocking ADO with hydralazine halted tumor growth, indicating the drug can disrupt a pathway glioblastoma uses to thrive.

These findings are promising but preliminary. The effects have been demonstrated in cell and animal models; clinical trials are required to determine whether hydralazine or optimized derivatives will benefit people with glioblastoma. Researchers emphasize caution and the need for careful testing to assess safety, dosing, and whether the drug penetrates brain tumors effectively.

The study also provides a clearer molecular explanation for hydralazine's longstanding use in pregnancy‑related hypertension such as preeclampsia. Understanding the drug's target opens opportunities to refine hydralazine or design new agents that selectively inhibit ADO, potentially reducing side effects while preserving therapeutic benefit.

"Hydralazine is one of the earliest vasodilators ever developed, and it's still a first‑line treatment for preeclampsia," says physician‑scientist Kyosuke Shishikura. "Pinpointing its molecular target gives us a route to safer, more selective therapies."

Chemist Megan Matthews adds that repurposing an established drug provides a head start for drug development: researchers can build on existing safety data while designing compounds that better target cancer cells. The study was published in Science Advances.

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