2016 Mystery Molecule


This molecule is at the heart of a recent scandal involving a prestigious medical journal. Can you guess what it is?

AACC May 2016 Molecule of the month

This drug was the first in a series of inhibitors of Factor Xa which could be given orally (unlike low-molecular-weight heparin, which must be injected). This alternative approach to oral anti-coagulation (instead of using the traditional drug, warfarin) is somewhat controversial. But the drug was in the news last month because of a letter published in the New England Journal of Medicine in February (New Eng J Med 2016;374:785-788). It concerned a clinical trial comparing the effectiveness of rivaroxaban versus warfarin for prevention of stroke in patients with atrial fibrillation. After the study (which showed similar effectiveness) was completed and published in the New England Journal in 2011, the FDA issued a recall notice for the POCT device which was used to measure the INR in the study. The recent letter was an attempt to show that it was unlikely that problems with the POCT device affected the study results but the authors neglected to mention that they had data comparing the POCT results with the central laboratory. This raised concern that the authors deliberately omitted mention of this in the letter for fear that there actually was a problem.


This molecule popped up in the news last month and generated controversy. Can you guess what it is?

April 2016 molecule-of-the-month

This drug was first synthesized in the 1970s in Latvia for use in livestock to prevent muscle ischemia. It inhibits fatty acid oxidation and improves oxygen delivery to tissues compromised by poor vasculature. The World Anti-Doping Authority classifies it as a performance-enhancing drug and bans its use. Tennis star Maria Sharapova claimed that she takes it for a heart condition (tradename: mildronate) but its presence caused her to fail a drug test at this year’s Australian Open. Subsequently, other Russian athletes were revealed to have tested positive, including two Olympic speed skaters and, on the eve of the world championships in the U.S., all of the Russian hockey players under 18 years of age. The fact that it is still only manufactured in Latvia may explain its apparent widespread use by Russian athletes.


An inventor who died last month used this molecule in several inventive ways. Can you guess what it is?

March Molecule

We tried to fool you and presented an image of the inactive form of insulin (a hexamer held together by zinc atoms that reminded us of a shamrock) but the answer was quickly guessed by Brett Holmquist on the AACC Artery. The inventor was Alfred Mann who died in February. A prolific scientist whose early career was in the aerospace industry, he was a pioneer in the development of insulin pumps. More recently, he was working on an inhalable form of insulin which was approved by the US Food and Drug Administration but has not been widely utilized.


This molecule will really get a workout this month. Can you guess what it is?


Its name comes from the genus of the cacao plant (Theobroma) which means food of the gods and it is responsible for the slightly bitter taste of dark chocolate (as well as cola drinks and some teas). It is very similar to theophylline and caffeine and has some of the pharmacological effects associated with those compounds. We hope that your Valentine’s Day was sweet, not bittersweet!


This molecule is the target in recently published reports describing the use of a new technology to treat a terrible disease. Can you guess what it is?

AACC Molecule January 2016

Three separate reports in Science described the use of the novel molecular gene editing machine CRISPR (an assembly of an endonuclease with a specific guide RNA that, when injected into a cell, directs the cell to excise the targeted exon) in a mouse model of Duchenne muscular dystrophy. This debilitating (and fatal) disease is caused by mutations in the gene for dystrophin, a large protein that holds the cell membrane to the underlying cellular cytoskeleton during muscle contraction. In Duchenne’s, the mutations cause the amount of protein to be markedly reduced, resulting in severe muscle damage. But not every exon is important for protein production as shown in Becker muscular dystrophy where mutations in other exons produce less severe reduction (and less severe muscle disease). Using an adenovirus to target the CRISPR machine to skeletal and cardiac muscle, production of dystrophin was restored with significant improvement in muscle function. CRISPR stands for clustered regularly interspaced short palindromic repeats (the target of endonucleases).