HA14-1

HA14-1 is a small-molecule antagonist of B-cell lymphoma 2 (Bcl-2) and Bcl-XL, originally identified as a BH3 mimetic. It binds to the hydrophobic surface pocket of anti-apoptotic Bcl-2 family members, disrupting their ability to sequester pro-apoptotic proteins like Bax and Bak, thereby promoting mitochondrial outer membrane permeabilization and the intrinsic apoptotic pathway. In addition to its primary target, HA14-1 has been shown to inhibit sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), which can lead to elevated cytosolic calcium levels and contribute to cell death through necrotic or apoptotic mechanisms. While HA14-1 has demonstrated potent in vitro cytotoxicity against various cancer cell lines, including gastric, colorectal, and B-cell malignancies, its therapeutic potential is limited by a notably short half-life and off-target effects. Consequently, it is primarily utilized as a research tool and a structural lead for the development of more stable analogs, such as sHA14-1, and novel microtubule-targeting agents like mHA11.

Other names

ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate