One Stop PROTAC Service

One Stop PROTAC Service 

Advantages of PROTAC

In Vitro Assays:

Western blot 

PROTACs downregulate the protein levels of their respective targets

ELISA

ARV-771 treatment for 16 h results in suppression of cellular c-MYC levels measured by ELISA.

IHC

Identification of the permeability of PRTC in Panc-1 cells

PRTC induces the ubiquitination and proteasomedependent degradation of the endogenous CREPT protein

Flow cytometry

Apoptosis was examined by propidium iodide (PI)/Annexin-V staining in combination with flow cytometry assay

Cell cytotoxicity

Effect of PROTAC on cell cytotoxicity

In Vivo Assays:

Example

Design and characterization of DCAF15 E3 ligase derived PROTAC to degrade BRD4 in vitro and in vivo

Reference

1. Li, L., Mi, D., Pei, H. et al. In vivo target protein degradation induced by PROTACs based on E3 ligase DCAF15. Sig Transduct Target Ther 5, 129 (2020). https://doi.org/10.1038/s41392-020-00245-0

2. Bondeson, D., Mares, A., Smith, I. et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat Chem Biol 11, 611–617 (2015). https://doi.org/10.1038/nchembio.1858

3. Raina, Kanak; Lu, Jing; Qian, Yimin; Altieri, Martha; Gordon, Deborah; Rossi, Ann Marie K.; Wang, Jing; Chen, Xin; Dong, Hanqing; Siu, Kam; Winkler, James D.; Crew, Andrew P.; Crews, Craig M.; Coleman, Kevin G. (2016). PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. Proceedings of the National Academy of Sciences, (), 201521738–. doi:10.1073/pnas.1521738113 

4. Ma, D., Zou, Y., Chu, Y., Liu, Z., Liu, G., Chu, J., … Chang, Z. (2020). A cell-permeable peptide-based PROTAC against the oncoprotein CREPT proficiently inhibits pancreatic cancer. Theranostics, 10(8), 3708–3721. doi:10.7150/thno.41677 

5. Ma, D., Zou, Y., Chu, Y., Liu, Z., Liu, G., Chu, J., … Chang, Z. (2020). A cell-permeable peptide-based PROTAC against the oncoprotein CREPT proficiently inhibits pancreatic cancer. Theranostics, 10(8), 3708–3721. doi:10.7150/thno.41677 

6. Zhao, Qiuye; Lan, Tianlong; Su, Shang; Rao, Yu (2019). Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule. Chemical Communications, (), 10.1039.C8CC07813K–. doi:10.1039/C8CC07813K 

7. https://www.arvinas.com/pipeline-programs/androgen-receptor