2-pyrrolinodoxorubicin

2-pyrrolinodoxorubicin (also known as AN-201 or p-DOX) is an exceptionally potent small molecule anthracycline derivative of doxorubicin. By substituting the amino group on the daunosamine sugar with a 2-pyrroline ring, the compound achieves a cytotoxic potency 500 to 1000 times greater than doxorubicin in vitro. Its mechanism of action is distinct from the parent compound; while doxorubicin primarily inhibits topoisomerase II, 2-pyrrolinodoxorubicin acts as a potent DNA alkylator that forms interstrand cross-links. These cross-links prevent DNA strand separation, thereby inhibiting essential cellular processes such as DNA unwinding by helicases and transcription by RNA polymerases. Furthermore, the drug is effective against multidrug-resistant cell lines that overexpress P-glycoprotein. It has been extensively studied as a cytotoxic "warhead" in targeted peptide-drug conjugates, including AN-238 (targeted to somatostatin receptors) and AN-207 (targeted to LHRH receptors), for the treatment of various solid tumors such as glioblastoma and renal cell carcinoma.

Other names

3'-deamino-3'-(2''-pyrroline-1''-yl)doxorubicin2-pyrrolino-doxorubicin