A focused PROTAC library hijacking cancer therapeutic target CDK6 was developed. A design principle as "match/mismatch" was proposed for understanding the degradation profile differences in these PROTACs. Notably, potent PROTACs with specific and remarkable CDK6 degradation potential were generated by linking CDK6 inhibitor palbociclib and E3 ligase CRBN recruiter pomalidomide. The PROTAC strongly inhibited proliferation of hematopoietic cancer cells including multiple myeloma and robustly degraded copy-amplified/mutated forms of CDK6, indicating future potential clinical applications.
HDAC6 (histone deacetylase 6) catalyses the deacetylation of non-histone substrates, and plays important roles in cell migration, protein degradation and other cellular processes.
Chitin-degrading bacterial strains were screened and tested for their ability to degrade shrimp-shell waste (SSW). Among the potential strains, B. cereus EW5 exhibited the highest chitin-degrading ability compared with other strains and produced 24 mg of reducing sugar per gram of dry SSW after 4 days of incubation. A TLC analysis of SSW biodegradation revealed that the chitosaccharides produced in the culture supernatant were mainly N-acetylglucosamine (GlcNAc) and chitobiose due to the isolate’s exolytic chitinase activity. The culture supernatant exhibited a high degree of antioxidant activity, as indicated by 83% DPPH, 99.6% ABTS, 51% hydroxyl radical scavenging activity and 0.34 reducing power. The formation of GlcNAc and chitobiose during biodegradation of SSW is considered to be the major contributor to the antioxidant activity. The EW5 culture supernatant also displayed inhibition of DNA damage, enhancing the reutilization value of SSW. This report presents the first description of fermented production of GlcNAc and DNA protective activity of culture supernatant from SSW by B. cereus.
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