Post by Symeres

Some of the most useful drugs we have started life as molecules made by something else. The latest candidate may be Nitenin, a furanoterpene from marine sponges collected off the southern coast of Portugal, near Sagres. Marine biologists at Sea4Us identified it as an analgesic, but one that works in an unusual direction. Most pain drugs block ion channels, while Nitenin opens them. Specifically, it potentiates slow voltage-gated potassium (Kv) currents in small-diameter dorsal root ganglion (DRG) neurons, the pain receptors that carry pain signals from the periphery to the spinal cord. More Kv current means a more hyperpolarized neuron, so the pain signal doesn't fire. Although the biology was clean, the chemistry was not. Natural furanoterpenes rarely make tractable drugs, so Sea4Us partnered with Symeres to find out whether this one could. The first step was to identify the minimal pharmacophore needed to retain analgesic activity. ADME work then flagged poor metabolic stability, and the team redesigned the scaffold to preserve activity while improving drug-like properties. The redesigned series hit new problems. Solubility was limited. solid-state behavior was awkward, and some of the structural fixes had introduced drug-drug interaction risk that hadn't been there before. Not to be defeated, the team went back to the design stage and engineered a whole new scaffold around all three constraints at once.  What came out the other side S072, a non-opioid pain killer that’s gone from seas sponge to clinical trials. 📷 courtesy of https://lnkd.in/eSCcWrXY