Calicheamicin (C09-0827-012)

Calicheamicin is an antitumor antibiotic and is a DNA synthesis inhibitor. It also is a cytotoxic agent that causes double-strand DNA breaks.In vitro activity:PF-06647263 (anti-EFNA4-ADC) is generated via conjugation of hE22 lysine residues to the AcButDMH-N-Ac-calicheamicin-γ1 linker-payload with an average drug-to-antibody ratio (DAR) of 4.6. PF-06647263 elicits antigen- and concentration-dependent cytotoxicity, as exposure to PF-06647263 for 96 hours results in cell death (EC50: ~1 ng/mL) .In vivo activity:PF-06647263 (0.27, 0.36 mg/kg) results in significant tumor regressions in TNBC xenografts. An ADC comprising a humanized anti-EFNA4 monoclonal antibody conjugated to the DNA-damaging agent calicheamicin achieves sustained tumor regressions in both TNBC and ovarian cancer PDX in vivo. Specifications and Purity: 98%. Molecular Formula: C55H74IN3O21S4. Molecular Weight: 1368.34. PubChem CID: 4489307. Isomeric SMILES: CCNC1COC(CC1OC)OC2C(C(C(OC2OC3C#CC=CC#CC4(CC(=O)C(=C3C4=CCSSSC)NC(=O)OC)O)C)NOC5CC(C(C(O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)OC7C(C(C(C(O7)C)O)OC)O)I)C)O)O.