This technology features a series of potent cytotoxic compounds derived from natural product scaffolds such as pederin, psymberin, and mycalamide. It incorporates a functionalized tetrahydropyran subunit and an N-acyl aminal linkage that work together to inhibit protein synthesis by binding to the 60S ribosomal subunit and displacing tedanolide. The detailed synthetic routes include steps like asymmetric allylation, stereoselective aldol reactions, and cycloadditions that enable the construction of their complex molecular architectures. Specific modification sites allow for the attachment of linkers to conjugate these compounds with antibodies, dendrimers, or liposomes for targeted delivery.
Description
What differentiates this approach is its precision in structural modification at key positions, such as C10 and C13 in the pederin framework and C8 and C11 in psymberin. These modifications create a platform that not only maintains high potency but also addresses general toxicity by optimizing selective drug delivery. The innovative synthetic strategy and adaptable linker conjugation enable exploration of structure-activity relationships, thereby enhancing therapeutic efficacy while mitigating off-target effects, offering a promising advancement in targeted cancer treatment.
Applications
- Targeted cancer therapeutics
- Antibody-drug conjugate development
- Precision oncology formulations
- Synthetic anticancer agent production
Advantages
- Potent anticancer activity through targeted inhibition of protein synthesis and induction of apoptosis.
- Enables selective delivery by conjugating to antibodies, dendrimers, or liposomes via functional linker modifications.
- Comprehensive synthetic methodologies facilitate the generation of diverse analogs for structure-activity optimization.
- Strategic functional modifications help reduce general toxicity, potentially improving the therapeutic window.
- Versatile design allows fine-tuning of therapeutic properties through controlled modifications at key positions.
IP Status
https://patents.google.com/patent/US9364555B2
