d9A-2
d9A-2 : Degrader (PROTAC) of SLC9A1
Structure
In Cells
(1
ratings)
In Model Organisms
(0
ratings)
Probe d9A-2 is in the process of SERP review.
Please continue to check back for new reviews and commentary.
SERP ratings and comments
SERP Ratings
In Cell Rating
SERP Comments:
CRBN recruiting PROTAC d9A-2 is currently (December 2023) the best available degrader of for studying the biology of SLC9 transporters, although it has certain drawbacks. Based on the data in the original publication, d9A-2 exhibits the most potent degradation of SLC9A1 as its main target. d9A-2 is further capable of potent degradation of SLC9A2 and SLC9A4 and shows also degradation of SLC9A5, SLC9A6, SLC9A7, SLC9A8 and SLC9B1. PROTACd9A-2 has been profiled against 11 members of SLC transporters (SLC9A/B) therefore the knowledge about its selectivity profile is insufficient. The corresponding negative control compound is missing (e.g. d9A-2 analogue with methylated imid). The mechanism of degradation was probed using CRBN knockout cell line, competition experiment with pomalidomide and via cotreatment with neddylation and proteasomal inhibitors. Since cytotoxicity has been evaluated only at a 72 hour time point (showing strong cytotox effect in some cell lines), it would be desirable for the potential users to determine the cytotoxic affects also at shorter time points, according to the indented use. With my comments above I don't want to diminish the important scientific contribution of the original publication witch showed for the first time that SLCs are amenable for PROTAC mediated degradation.
(last updated: 28 Dec 2023 )