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Calicheamicin

CAS No. : 108212-75-5

產(chǎn)品活性：Calicheamicin, an antitumor antibiotic, is a cytotoxic agent that causes double-strand DNA breaks. Calicheamicin is a DNA synthesis inhibitor.

研究領(lǐng)域：Cell Cycle/DNA Damage  |  Antibody-drug Conjugate/ADC Related  |  Anti-infection  |  Apoptosis

作用靶點(diǎn)：DNA Alkylator/Crosslinker  |  ADC Cytotoxin  |  Bacterial  |  Apoptosis  |  Antibiotic

In Vitro: 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= appr 1 ng/mL). CMC-544, consisting of a humanized CD22 Ab linked to calicheamicin, is effective in pediatric primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells in vitro. CMC-544 induces cell death in various ALL cell lines in a dose- and time-dependent way, with IC₅₀ values ranging from 0.15 to 4.9?ng/mL. CMC-544 (10?ng/mL) is effective and specific in primary BCP-ALL cells. In CMC-544-treated cells, the level of CD22 has decreased relative to that on G5/44-treated cells and continued to decrease.

In Vivo: 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. PF-06647263 (0.27, 0.36 mg/kg) results in significant tumor regressions in TNBC xenografts.

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