UNBS5162

UNBS5162 is a small molecule derivative of amonafide in the naphthalimide chemical class[1][5]. It acts as a pan-antagonist of chemokine ligand (CXCL) expression, exerting anti-angiogenic and antitumor activity in preclinical studies. UNBS5162 intercalates into DNA and potently suppresses the expression of several proangiogenic CXCL chemokines, disrupting CXC chemokine family signaling which is involved in angiogenesis and tumor progression[1][5][6][7]. The drug also inhibits tumor cell proliferation, migration, and invasion, and promotes apoptosis in assorted cancer cell lines, including prostate, breast (triple-negative and ER-positive), gastric, colon, lung, and retinoblastoma[2][3][4][5][6][7]. Mechanistically, UNBS5162 downregulates the PI3K/AKT/mTOR signaling pathway, increases proapoptotic proteins (Bax, Bim, active caspase-3), and decreases anti-apoptotic protein Bcl2[2][3][4][7]. Phase I clinical trials in patients with advanced solid tumors and lymphoma tested intravenous administration, but dose escalation was terminated due to cardiac (QTc) toxicity[5].

Other names

1-(2-(2-(dimethylamino)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)ureaUNII-JY9JF7D78NUNII-JY-9JF7D78NUNII-JY 9JF7D78NUrea, N-(2-(2-(dimethylamino)ethyl)-2,3-dihydro-1,3-dioxo-1H-benz(de)isoquinolin-5-yl)-