NO Puns

Oct 26, 2023

The title is itself a pun because NO stands for nitric oxide, a soluble gas that controls a huge number of critically important biological functions from vasodilation and platelet function to penile erections. The puns about NO in the scientific literature are endless, literally endless: NO sex, NO reward, NO to heart disease, and NO hope, to name but a very few.

In 1992 the journal science made NO the Molecule of the Year in recognition of its versatility with a prominent pun on the title page, as shown below.

But NO joke, 😂 the reason to mention nitric oxide in this blog post is because our lead small molecule, RRx-001 (nibrozetone) releases a lot of it—but only under conditions of low oxygen or hypoxia/ischemia.

This differentiates RRx-001 (nibrozetone) from other FDA approved nitric oxide donors like nitroglycerin or sodium nitroprusside that release NO systemically. Systemic release is potentially problematic because of side effects that may include headaches, low blood pressure (hypotension), and methemoglobinemia.

The fact that RRx-001 (nibrozetone) releases NO locally only when and where hypoxia/ischemia are present means that it is responsible for NO headaches, NO hypotension, and NO methemoglobinemia (ba-dum-tss! .)

It also means that RRx-001 (nibrozetone) is potentially very well suited for treatment of vascular and cardiac disease states, as several preclinical studies suggest, because NO is cardio- and vasculoprotective.

If healthy blood vessels are smooth like Teflon, then unhealthy ones are rough and sticky like Velcro. However, NO ‘teflonizes’ blood vessels or, in other words, it makes them—wait for it—NO stick.

So, in summary, while RRx-001 (nibrozetone) has been developed primarily in cancer, its ideal use is potentially as a cardiovascular agent.

And now, as this is the last sentence, we promise NO more puns.