LCS-1, a superoxide dismutase 1 (SOD1) inhibitor, effectively inhibits the enzymatic activity of SOD1 with an IC50 value of 1.07 μM. Additionally, LCS-1 triggers both early and late-stage apoptosis in multiple myeloma (MM.1S) cells [1] [2] [3].

LCS-1 (1-10000 nM; 24 hours) is selective cytotoxic to both bloom syndrome gene product (BLM) -proficient and BLM-deficient HCT116 cells [1]. LCS-1 shows growth inhibitory effect on 10/27 adenocarcinoma cell lines (median IC 50 =0.20 μM; such as H23, H2347, HCC827 cell lines) and normal human bronchial epithelial (NHBE) cells (IC 50 =2.66 μM) [2]. LCS-1 (0, 1.25, 2 μM; 4 h) in a concentration-dependent manner triggers significant inhibition of SOD1 enzymatic activity in multiple myeloma (MM) cells [3]. LCS-1 (0, 1.25, 2.5, 5 μM; 48 h) in a dose-dependent manner reduces the viability of various MM cell lines, including MM.1R (Dexamethasone-resistant), Dox40 (Doxorubicin-resistant), or LR5 (Melphalan-resistant) cell lines [3]. LCS-1 (48 h) has IC 50 values of 2.5 and 4.6 μM for cell viability of ANBL6-WT (Bortezomib-sensitive) and ANBL6-BR (Bortezomib- resistant) cells, respectively [3]. LCS-1 (1.25 μM; 16 h) induces a significant increase in ROS levels and O 2 levels in MM.1S cells [3]. LCS-1 (1.25 μM; 16 h) shows a significant decrease in GSH/GSSG ratio in MM.1S cells [3]. LCS-1 (1.25 μM; 24h) induces the release of mitochondrial cytochrome-c into the cytosol, and enriches the proteins (HSP60/CLPP) mediating mtUPR signaling in MM.1S cells [3]. LCS-1-induced O 2 (1.25 μM; 5 h) triggers a marked decrease in both RP 2 CP and RP 1 CP forms of 26S proteasomes [3]. LCS-1 (2 μM; 16 h) induces the early- and late-stage apoptosis of MM.1S cells [3]. LCS-1 (0, 0.5, 1, 1.5, 2 μM) upregulates p53/p21 signaling, as well as downregulates survival pathway proteins MCL-1, BclxL, or c-Myc in MM.1S cells [3]. LCS-1 (0, 4, 8, 16, 24 h; 2 μM) shows a rapid and robust induction of mitochondrial unfolded protein response (UPR) proteins (BIP, PERK, phosphorylated eIF2α, or a lectin protein calnexin) in MM.1S and ANBL6-BR cells [3]. Cell Viability Assay [1] Cell Line: BLM-proficient and BLM-deficient HCT116 cells Concentration: 1-10000 nM Incubation Time: 24 hours Result: Had IC 50 values of 1462 nM and 24.92 nM for the viability of BLM-proficient and BLM-deficient HCT116 cells, respectively. Western Blot Analysis [3] Cell Line: MM.1S and ANBL6-BR cells Concentration: 2 μM Incubation Time: 16 hours Result: Decreased the expression of cell-cycle regulatory proteins (cyclin-B1, CDC25C, and CDC2). Western Blot Analysis [3] Cell Line: MM.1S cells Concentration: 0, 0.5, 1, 1.5, 2 μM Incubation Time: Result: Upregulated p53/p21 signaling, as well as downregulated survival pathway proteins MCL-1, BclxL, or c-Myc. Western Blot Analysis [3] Cell Line: MM.1S cells Concentration: 2 μM Incubation Time: 0, 4, 8, 16, 24 hours Result: Showed a rapid and robust induction of UPR proteins (BIP, PERK, phosphorylated eIF2α, or a lectin protein calnexin).

LCS-1, administered intraperitoneally at a dose of 20 mg/kg diluted in saline every other day for 14 days, effectively inhibits the growth of multiple myeloma (MM) and extends survival in 5-week-old female CB17 SCID mice with MM.1S tumors of 100 mm^3 volume. This treatment regimen demonstrated significant anti-MM activity and survival benefits in the animal model.