Hu, Zhiye published the artcileNovel class of 7-Oxabicyclo[2.2.1]heptene sulfonamides with long alkyl chains displaying improved estrogen receptor α degradation activity, Category: isoquinoline, the main research area is estrogen receptor breast cancer selective downregulators SAR; Breast cancer; Estrogen receptor; Long alkyl chains; Selective estrogen receptor downregulators; Structure-activity relationships.
Hormone therapy is widely used in clinic for breast cancer treatment, such as tamoxifen, but long-term use can cause drug resistance. In this regard, a strategy based on small mol.-induced protein degradation, i.e. selective estrogen receptor downregulator (SERD), might be an effective alternative to hormone therapy for breast cancer. However, most of the SERD candidates involve very limited scaffolds and are still in clin. trials, and none of them has been approved for marketing. In this study, a series of novel 7-oxabicyclo[2.2.1]heptene sulfonamide (OBHSA) derivatives with long alkyl chains were identified as novel SERDs. We found that the position and the length of alkyl side chain have significant effect on the biol. activity of the SERD compounds and with the six-carbon side chain was the best. Among them, compounds 23a and 36 displayed potent inhibitory activity against MCF-7 breast cancer cell line with IC50 values of 0.84μM and 0.77μM, resp., as well as excellent ERα degradation activity. Primary mechanism study indicated that the degradation of ERα is mediated through proteasome-mediated process. Flow cytometry anal. of apoptosis of 36 suggested that the effect of this type compounds on MCF-7 cells is associated with apoptosis. As such, these compounds have shown potential to become promising leads for the development of highly efficient SERDs for drug-resistance breast cancer therapies.
European Journal of Medicinal Chemistry published new progress about Antitumor agents (drug resistance breast cancer therapies). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Category: isoquinoline.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem