Pelcitoclax (APG-1252, BM-1252) is a potent dual specific Bcl-2/Bcl-xL inhibitor with Ki of < 1 nM, shows potent antitumor effects with minimal platelet toxicity.
Pelcitoclax (APG-1252, BM-1252) changes to its reactive metabolite, named APG-1252-M1, in vivo can disrupt the anti-apoptotic function of these proteins with potent antitumor effects.
APG-1252 is >10- times less active than APG-1252-M1 in cell growth assay in a panel of small cell lung cancer (SCLC) cell lines.
APG-1252-M1 induces Bax/Bak-dependent apoptosis in MEF/MCL1−/− model cell line.
APG-1252 is >30-times less effective in platelet killing than BM-1252-M1 in animals. APG-1252-M1 exerts nanomolar single agent activity in a small subset of colorectal cancer (CRC) cell lines and synergizes with MEK inhibitor trametinib in a large subset of CRC cell lines.
APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo, has synergistic anticancer activities against advanced nasopharyngeal carcinoma (NPC).