《Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines》 was published in European Journal of Medicinal Chemistry in 2020. These research results belong to Zhang, Xuan; He, Yonghan; Zhang, Peiyi; Budamagunta, Vivekananda; Lv, Dongwen; Thummuri, Dinesh; Yang, Yang; Pei, Jing; Yuan, Yaxia; Zhou, Daohong; Zheng, Guangrong. Quality Control of Methyl 3-bromopropanoate The article mentions the following:
Targeting BCL-XL via PROTACs is a promising strategy in reducing BCL-XL inhibition associated platelet toxicity. Recently, we reported potent BCL-XL PROTAC degraders that recruit VHL or CRBN E3 ligase. However, low protein expression or mutation of the responsible E3 ligase has been known to result in decreased protein degradation efficiency of the corresponding PROTACs. To overcome these mechanisms of resistance, PROTACs based on recruiting alternative E3 ligases could be generated. Thus, we designed and synthesized a series of PROTACs that recruit IAP E3 ligases for BCL-XL degradation Among those PROTACs, compound 8a(I) efficiently degrades BCL-XL in malignant T-cell lymphoma cell line MyLa 1929 while CRBN-based PROTACs that have high potency in other cancer cell lines show compromised potency, likely due to the low CRBN expression. Moreover, compared with the parent compound ABT-263, PROTAC 8a shows comparable cell killing effects in MyLa 1929 cells whereas the on-target platelet toxicity is significantly reduced. Our findings expand the anti-tumor spectra of BCL-XL degraders and further highlight the importance of selecting suitable E3 members to achieve effective cellular activity. In addition to this study using Methyl 3-bromopropanoate, there are many other studies that have used Methyl 3-bromopropanoate(cas: 3395-91-3Quality Control of Methyl 3-bromopropanoate) was used in this study.
Methyl 3-bromopropanoate(cas: 3395-91-3) belongs to bromides. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents.Quality Control of Methyl 3-bromopropanoate
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary