ZLDI-8

ZLDI-8 is a **small molecule inhibitor** of the Notch activating/cleaving enzyme **ADAM-17 (A disintegrin and metalloproteinase domain 17, also known as TACE)**[1][4][3][5][6]. ZLDI-8 inhibits ADAM-17-mediated cleavage of Notch proteins, leading to decreased Notch signaling, and thereby downregulates the expression of pro-survival, anti-apoptosis, and epithelial-mesenchymal transition (EMT)-related proteins[1][4][3][5]. ZLDI-8 has been shown to enhance the susceptibility of hepatocellular carcinoma (HCC) and chemotherapy-resistant non-small cell lung cancer (NSCLC) cells to chemotherapeutic agents such as sorafenib, etoposide, and paclitaxel both in vitro and in vivo, without significant antitumor effect on its own[4][3][5]. Additional effects include the inhibition of the Akt pathway, downregulation of HIF-α, ERK1/2, MMP-9, and MMP-2, and modulation of the integrin pathway involving FoxC2, Integrinβ1, Integrinβ3, and ILK[2]. ZLDI-8 is also reported as a competitive and irreversible inhibitor of the tyrosine phosphatase Lyp[1]. ZLDI-8 was discovered using virtual molecular docking approaches[4][3]. It is primarily a research compound with no known clinical approval[1][4][5].

Other names

ZLDI-8ZLDI8ZLDI 8IAC-8IAC8IAC 8inhibitor of ADAM-17 compound No. 8