Nav: Home

Research paves way for new source for leukemia drug

March 20, 2019

CORVALLIS, Ore. - Chemistry researchers at Oregon State University have patented a method for making anti-leukemia compounds that until now have only been available via an Asian tree that produces them.

The synthesis of cephalotaxine and homoharringtonine (HHT) paves the way toward less-expensive, more readily available leukemia drugs whose production is not subject to the risks and inefficiencies associated with harvesting natural sources.

Also, the synthesis of cephalotaxine opens the door to preparing other, structurally related compounds for evaluation as potential new cancer drugs.

"We want to partner with industry so we don't have to grow trees to get this anymore," said corresponding author Christopher Beaudry, associate professor of chemistry in OSU's College of Science. "And maybe we can come up with a more potent protein translation inhibitor, or a more selective inhibitor. There's also a chance this molecule can find application in blocking bacterial protein synthesis, which would be useful for treating antibiotic-resistant pathogens."

Findings were published in Angewandte Chemie.

HHT, also known as Synribo or omacetaxine mepesuccinate, is used to treat chronic myeloid leukemia, one of four main types of the disease.

Historically, HHT has been made by adding an ester to cephalotaxine, an alkaloid derived from the leaves of an Asian tree: the plum yew. And the only way to get more cephalotaxine was to plant more plum yews.

That's problematic, Beaudry said.

"Trees don't grow very fast," he said. "And any kind of agricultural problem can affect production of the material. By using chemical synthesis, we can start with commodity chemicals to prepare cephalotaxine, and we will further optimize the process to make it commercially viable."

Leukemia is a type of cancer that originates in the blood-forming cells of the bone marrow. Nearly 200,000 people in the U.S. are diagnosed with leukemia each year.

Myeloid leukemias, which are also called myelocytic, myelogenous or non-lymphocytic leukemias, start in early myeloid cells. Myeloid cells are what eventually become platelet-making cells and white blood cells other than lymphocytes.

Chronic myeloid leukemia develops slowly, and most patients can live with it for several years, but it's harder to cure than the acute form of the disease. It's characterized by a chromosome abnormality that results in a protein overproduction, leading to the proliferation of the cancer cells.

Chronic myeloid leukemia is treated with drugs, such as Gleevec, that bind to a cancer-causing protein and inactivate it - until the cancer mutates and the drug doesn't work anymore, which is where HHT comes in. HHT shuts off production of all proteins that the fast-growing leukemia cells require.

In addition, HHT holds promise for thwarting chronic myeloid leukemia stem cells, as well as for combating other cancer cell lines.

Beaudry and graduate student Xuan Ju used an oxidative ring-opening of a furan, a type of organic compound, to trigger the HHT synthesis via a reaction known as a spontaneous transannular Mannich cyclization.

"From start to finish - all nine steps from the chemical we buy - the yield is greater than 5 percent, which sounds terrible but is actually quite good," Beaudry said. "Typically the yield for any process would be much lower - think about how much tree mass is required to make HHT - and we think we can make further improvements as well."
-end-
The National Science Foundation and OSU supported this research.

Oregon State University

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.