Coumarin occurs naturally in a variety of plants, such as lentils, sweet sawdust, vanilla grass, and sweet grass. Coumarin has a simple structure, benzopyrone, associated with different reaction centers. Coumarins are further subdivided into different classes: simple coumarins, pyranocoumarins, furanocoumarins, dicoumarins and isocoumarins. Coumarin derivatives are an important class of natural plant metabolites with various biological activities. They can also be synthesized artificially, and various synthetic coumarin derivatives (azoles, sulfonyls, furans, pyrazoles, etc.) have shown good anticancer, antitumor and antiproliferative activities. Coumarin derivatives are not only effective anticancer agents, but also possess minimum side effects. Based on different substitution patterns, these potential active substances show a great ability to modulate potential anticancer activities.
Nested Therapeutics’ lead program, NST-628, is an oral, brain-penetrant pan-RAF-MEK non-degrading molecular glue that lacks paradoxical pathway activation through the prevention of RAF paralog heterodimerization. By inhibiting the phosphorylation and activation of MEK by RAF, NST-628 targets a critical step in the RAS/RAF/MAPK signaling pathway. Preclinically, NST-628 results in broad efficacy, high tolerability, CNS activity across various RAS- and RAF-driven tumor models, and has the potential to deliver transformative clinical benefits both as a monotherapy and as a key component in combination therapies. Now, NST-628 has advanced to a Ph. I trial in patients with refractory MAPK pathway mutated/dependent advanced solid tumors. Chemenu has been working to develop more compounds for drug discovery. Here are the building blocks we can provide.
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