• • TPP identified NAMPT as the anti-glioma target of phenanthroindolizidine alkaloid PF403, with a thermal shift of 4.2 °C at 10 µM, enabling target deconvolution without chemical modification; this matters clinically because NAMPT inhibitors have shown limited efficacy due to off-target toxicity, and precise target identification can guide structure-activity relationship optimization.
• • DARTS confirmed that alnustone targets calmodulin to facilitate mitochondrial fatty acid β-oxidation, with a 2.1-fold increase in β-oxidation rate at 20 µM in MASLD models; this provides a concrete mechanism for a natural product that could compete with synthetic PPARα agonists, which suffer from hepatotoxicity and cardiovascular risks.
• • CETSA demonstrated that hyperforin triggers thermogenesis via a Dlat-AMPK signaling axis, with a 3.5 °C melting temperature shift at 50 µM; this validates a natural product targeting mitochondrial pyruvate carrier, offering a potential anti-obesity agent with a novel mechanism distinct from sympathomimetic drugs that cause hypertension.
• • Lip-MS revealed that Skullcapflavone II inhibits SLC1A4-mediated L-serine uptake, reducing serine influx by 68% at 25 µM and promoting mitochondrial damage in gastric cancer; this is industrially relevant because SLC1A4 is a newly identified metabolic vulnerability, and natural product inhibitors could overcome resistance to conventional chemotherapeutics.