SRJ23

SRJ23 is a **semisynthetic derivative** of andrographolide, itself a natural product isolated from *Andrographis paniculata*. SRJ23 is a **bicyclic lactone** developed as a potential anticancer agent. The compound demonstrates selective growth inhibitory effects against several cancer cell lines, notably including prostate cancer and T-cell acute lymphoblastic leukemia. Mechanistically, SRJ23 induces **cell cycle arrest** (G2/M in PC-3 prostate cells, and G1 in DU145, LNCaP, MCF-7, and HCT-116 cells) by downregulating cyclin-dependent kinase (CDK) 1 or CDK4 and cyclin D1, depending on the cell type[1][3]. SRJ23 further activates mitochondrial apoptosis via induction of caspase-8, caspase-9, and Bax, with downregulation of Bcl-2[1]. Crucially, SRJ23 acts as a **selective inhibitor of the GDP-GTP nucleotide exchange on K-Ras**, which inhibits Ras activation and downstream MAPK signaling. It directly targets Ras, with greater potency against K-Ras than H-Ras or N-Ras, and disrupts oncogenic Ras signaling by binding allosteric sites[2][4][6]. SRJ23 shows **synergistic antileukemic effects in vitro** when combined with hydroxyurea against T-ALL cells[2][5].

Other names

3,19-(3-chloro-4-fluorobenzylidene)andrographolide