EBC-46 is a compound derived from the seeds of the blushwood (Fontainea picrosperma) tree, a native species found exclusively in rainforests in northeast Australia. It was only discovered a decade ago through automated drug screening by QBiotics, an Australian life sciences company.

EBC-46 is known to bind with key enzymes known as protein kinase C, or PKC, which play a crucial role in cell signaling. They influence various cellular functions, including cell growth, differentiation, apoptosis (programmed cell death), and immune responses. Many cellular processes therefore rely on PKC, but many are also involved with major diseases, such as AIDS (the advanced stage of HIV), cancer and even Alzheimer’s.

This is why Stanford-affiliated researchers have been exploring EBC-46 across various medical contexts, including HIV.

In this case, the need for effective virus eradicating strategies is of primary importance. Since the virus emerged in humans in the final decades of the 20^th century, nearly 90million people have been infected, and around half of those people have died, according to the Joint United Nations Programme on HIV/AIDS.

Across the world, around 40 million people are living with the infection, and nearly two million people become infected each year.

At present, antiretroviral therapies (ARTs) have managed to transform a once-lethal disease into a chronic, manageable condition, but ARTs come with drawbacks for patients. They are expensive, tend to have low access, and require lifetime adherence.

“Part of the solution to the global HIV problem is addressing the 40 million people who are HIV positive,” Paul Wender, the Bergstrom Professor of Chemistry at Stanford’s School of Humanities and Sciences and lead author said in a statement.

“Easing the medication burden and economic losses posed by the current HIV regimen, especially in developing countries, is critical.”

During their new study, Wender and colleagues wanted to examine EBC-46’s value as a “latency reversing agent”, which basically kickstarts certain pathways in latent cells infected by the HIV virus. Latent cells serve as a “redoubt” for HIV as it faces the host’s immune attacks and medical treatments, such as ART. If these cells could be ferreted out and exposed to treatments, then we would be much closer to eliminating the virus in an infected person.

The team exposed latent HIV-infected cells to 15 analogs of EBC-46 – compound that is chemically similar to the tree-derived compound which could be even more capable of kicking latent cells into action.

Previously, Wender and colleagues contributed significantly to making EBC-46 more widely available by debuting a novel way to synthetically produce it in bulk in a laboratory. This opened the door for wide-ranging research and the production of non-natural and potentially superior analogs.

The team found that some of the analogs used in the new HIV-focused study actually reversed latency in 90 percent of the treated cells. This amounts to an incredible four-fold increase over the most powerful latency reversing agent used to date – bryostatin – which only activates around 20 percent of treated cells.

“Our studies show that EBC-46 analogs are exceptional latency reversing agents, representing a potentially significant step toward HIV eradication,” Wender added. 

These results build on a growing body of work concerning EBC-46. A medication based on it received approval by the US Food and Drug Administration in 2024 for treating soft tissue sarcomas, a form of cancer in humans. This approval came after its approved use in ventenary medicine where a drug had an 80 percent cure rate for mast cell tumors in dogs.

Wender and colleagues have now moved their research into animal models for HIV, with the goal of eventually conducting human trials.

“The fact that we may be able to make a dramatic difference in people’s lives with EBC-46 is what keeps us up late at night and gets us up early in the morning,” Wender concluded. 

The paper is published in Science Advances.