Ki: 6 nM for BCL-2 TR-FRET
A-1331852 is a potent and selective inhibitor of BCL-XL.
Apoptosis is reported to be regulated by a family of closely related proteins exemplified by B cell lymphoma protein 2 (BCL-2), which is the first discovered family member. BCL-2 family proteins are divided by one to four BCL-2 homology motifs and can be further subdivided into pro- and antiapoptotic subsets.
In vitro: A-1331852 was identified as a potent BCL-XL inhibitor demonstrating cellular activity 10- to 50-fold more potent than its analog A-1155463 and the previouly reported BCL-XL inhibitor, navitoclax, respectively. Moreover, A-1331852 could selectively disrupt BCL-XL–BIM complexes and induce the apoptosis hallmarks in BCL-XL–dependent Molt-4 cells with median IC50 values in the low nanomolar range but did not affect MEF cells without BAK or BAX .
In vivo: Previous animal study found that A-1331852 could demonstrate antitumor efficacy in the Molt-4 xenograft model, such as tumor regressions as a single agent. In addition, in the NCI-H1963.FP5 xenograft model of SCLC, it was found that A-1331852 combined with venetoclax was able to recapitulate the efficacy of navitoclax .
Clinical trial: Up to now, A-1331852 is still in the preclinical development stage.
 Leverson JD et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med. 2015 Mar 18;7(279):279ra40. doi: 10.1126/scitranslmed.aaa4642.
|Storage||Store at -20°C|
|Solubility||Soluble in DMSO|
|Chemical Name||3-(1-(adamantan-1-ylmethyl)-5-methyl-1H-pyrazol-4-yl)-6-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)picolinic acid|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|