SLMP53-2 is a mutant p53 reactivator that restores the wild-type-like conformation and DNA-binding ability of mutp53-Y220C through enhanced interaction with Hsp70, thereby reinstating p53's transcriptional activity. This compound induces cell cycle arrest, apoptosis, and endoplasmic reticulum (ER) stress, displaying antitumor activity [1] [2].

SLMP53-2, at concentrations ranging from 3.12 to 50 µM over 48 hours, inhibits the proliferation of HuH-7 and HCC1419 cells with similar IC50 values. Its growth inhibition activity is significantly reduced in non-tumorigenic HFF-1 cells (IC50 of 50 µM) [1]. Additionally, treatment with SLMP53-2 at 14 to 28 µM for 48 to 72 hours induces cell cycle arrest at the G0/G1 phase and apoptosis in HuH-7 cells [1]. A concentration-dependent inhibitory effect on colony formation in HuH-7 cells is observed with SLMP53-2 at 0.9 to 14 µM over 14 days [1]. At 28 µM for 24 hours, SLMP53-2 elevates levels of nuclear XBP1 protein, spliced XBP1 (sXBP1) mRNA, and phosphorylated eIF2α in HuH-7 cells [1]. Exposure to SLMP53-2 at 14 µM for 16 to 48 hours increases protein levels of MDM2, p21, GADD45, BAX, and KILLER, while downregulating survivin and VEGF, with these effects abrogated in HuH-7 p53KO cells [1]. Furthermore, SLMP53-2 at 1.5 µM sensitizes HuH-7 cells to Sorafenib [1].

SLMP53-2 (50 mg/kg; i.p., five doses) significantly reduced tumor volume and weight in nude mice bearing HuH-7 xenografts, with no evident toxic side effects [1].