What is TOFA (5-tetradecyloxy-2-furoic acid)?

Your body makes its own fat. Cells build fatty acids from scratch, all day long. But what if you could switch that off? That is exactly what a small molecule called TOFA does. Its full name is a mouthful: 5-tetradecyloxy-2-furoic acid. Almost everyone just says TOFA.

Chemists also file it under the CAS number 54857-86-2. You may see older lab names too, like RMI-14514 and MDL-14514. Its formula is C₁₉H₃₂O₄, and it weighs about 324.5 daltons. Picture a small ring with an acid group on one end and a long, greasy tail on the other. That tail lets TOFA slip right into a cell. Once inside, it gets to work.

How TOFA works

First, a quick look at what TOFA gets in the way of. Making fatty acids starts with one key step. An enzyme called acetyl-CoA carboxylase, or ACC, turns a molecule named acetyl-CoA into one named malonyl-CoA. This is the slow, “no going back” step that starts the whole process. Stop ACC, and the cell can’t make new fat.

TOFA stops it in a clever way. Here is the twist: TOFA by itself does nothing. The cell has to change it first. Once TOFA enters a cell, the cell turns it into a new form called TOFyl-CoA. And that new form is the real weapon.

Now, cells already have a natural “off switch” for ACC. When they have plenty of fat on hand, that switch tells ACC to slow down. TOFyl-CoA looks just like that off switch. So it fools the cell. The cell thinks it has enough fat, so it quits making more. Scientists say the effect is strong, and it comes and goes with the dose. Use more, and you get more of an effect. Take it away, and ACC starts back up.

There is another well-known blocker called cerulenin. It also shuts down fat-making, but at a later step. Scientists often use both. That way they can see what happens when they cut the process off early versus late.

From a heart drug to a lab tool

TOFA did not start as a lab chemical. Back in the 1970s, scientists tested it as a drug to lower fat in the blood. Early tests showed that it did cut fat-making in cells and animals. It never made it to market as a medicine. But it had one big thing going for it: a clean, clear way of working. That made it perfect for research.

Today, scientists reach for TOFA all the time. They use it in liver cells, fat cells, stem cells, and more. The question is always the same. What happens to a cell when it can’t make its own fat? TOFA gives them an easy way to find out.

TOFA and cancer research

Cancer is where TOFA really shines as a tool. Here is why. Cancer cells grow fast. To grow, they need a lot of fat to build new parts. So many tumors crank up their fat-making. In fact, ACC runs high in cancers of the breast, prostate, and other tissues. That gives scientists an idea. What if you cut off the fat? TOFA lets them try.

And the results are striking. TOFA can slow down cancer cells. It can even push them to die. In prostate cancer cells, TOFA cut fat-making and set off the cell’s self-destruct switch. In cholangiocarcinoma, a hard-to-treat bile duct cancer, TOFA stalled the cells and made them die. This worked in both dishes and animals. Scientists have looked at ovarian cancer too.

Now, this does not make TOFA a cancer cure. Not at all. But it does point to a real idea: starve the tumor of the fat it needs.

Other things TOFA can do

TOFA does more than fight cancer in the lab. Scientists have used it to study swollen airways in asthma. They have used it to study how the body makes insulin. And here is a surprise: it can help nerve cells grow tiny new branches. That finding even led to patents that name it for Alzheimer’s disease.

The bottom line

TOFA is small, but it does a big job in the lab. It shuts off the cell’s fat-making by tricking one key enzyme. That lets scientists ask sharp questions. What does fat-making really do? And what breaks when you take it away? TOFA is sold for research only, not as a medicine. Even so, it stays a go-to tool wherever fat and disease meet.

Frequently asked questions

What does TOFA stand for? TOFA is short for 5-tetradecyloxy-2-furoic acid. You may also see it called RMI-14514 or MDL-14514. Its long chemical name is sometimes written as 5-(tetradecyloxy)-2-furancarboxylic acid.

How does TOFA work? TOFA blocks an enzyme called acetyl-CoA carboxylase (ACC). ACC runs the first, key step in making fatty acids. When a cell takes in TOFA, it turns it into a form called TOFyl-CoA. That form switches ACC off, so the cell stops making new fat.

Is TOFA a drug? No. Scientists tested it as a fat-lowering drug in the 1970s, but it never became a medicine. Today it is sold only as a research chemical. The label says “for research use only.” It is not meant for people to take.

Why does cancer research use TOFA? Cancer cells often make a lot of fat to fuel fast growth, and ACC runs high in many tumors. TOFA lets scientists shut that off and see what happens. In prostate cancer, bile duct cancer, and other tests, TOFA slowed cancer cells and made them die. That makes it a handy tool for studying fat-based cancer treatments.

How is TOFA different from cerulenin? Both stop the body from making fat, but at different points. TOFA hits an early step (the ACC enzyme). Cerulenin hits a later step (an enzyme called fatty acid synthase). Scientists often use both, so they can compare what breaks at each stage.

What are the basic facts about TOFA? TOFA’s formula is C₁₉H₃₂O₄. It weighs about 324.5 daltons. Its CAS number is 54857-86-2. It is a small molecule that slips easily into cells. Labs usually buy it at high purity and mix it with a liquid called DMSO for testing.