FZ-AD005 

FZ-AD005 is a DLL3-targeting antibody-drug conjugate (ADC) with high selectivity, composed of the anti-DLL3 antibody FZ-A038 (HY-P990896), a dipeptide linker (Val-Ala), and DXd (HY-13631D). The K_d value of FZ-AD005 for human DLL3 ranges from 13.29 to 58.3 pmol/L. After binding to DLL3 on the cell surface, FZ-AD005 mediates endocytosis, and the payload DXd is released via cleavage by lysosomal cathepsins. DXd inhibits topoisomerase TopI to induce double-strand DNA breaks, cell cycle arrest and apoptosis, and FZ-AD005 exhibits bystander killing activity against adjacent DLL3-negative cells. FZ-AD005 shows stable circulation in vivo, has good tolerance and acceptable pharmacokinetic profiles in rats and cynomolgus monkeys, and effectively inhibits the growth of DLL3-expressing tumor cells. FZ-AD005 serves as a promising candidate molecule for research on small cell lung cancer and human neuroendocrine prostate cancer^[1][2].

FZ-AD005 (1 μg/mL; 144 hours) exhibits a strong bystander killing effect, eliminating both DLL3-positive NCI-H82 cells and DLL3-negative Ramos cells in a Transwell coculture system^[1].
FZ-AD005 (0.78-100 nmol/L human DLL3) exhibits high affinity binding to human DLL3 (K_d=58.3 pmol/L) and FcRn (K_d=29 nmol/L), but very low affinity for FcγRI, FcγRIIa, and FcγIIIa, when tested in a biolayer interferometry assay^[1].
FZ-AD005 (100 μg/mL; 7 days) is highly stable in human plasma, with only ~0.7% DXd released after 7 days of incubation at 37°C^[1].
FZ-AD005 (200 pmol; 48 hours) rapidly internalizes into DLL3-expressing cells within 30 minutes, traffics to lysosomes, and releases DXd in a time-dependent manner when tested over 48 hours^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

FZ-AD005 (2.5-10 mg/kg; intravenous injection; single administration) induces dose-dependent tumor growth inhibition in female NOD/SCID mice bearing NCI-H889 small cell lung cancer (SCLC) xenografts; its tumor growth inhibition (TGI) rates range from 86.21% to 95.54% at single intravenous doses of 2.5, 5, and 10 mg/kg^[1].
Single intravenous administration of FZ-AD005 (1.5-6 mg/kg; intravenous injection; single dose) at doses of 1.5, 3 and 6 mg/kg induces complete tumor growth inhibition in male NOD/SCID mice inoculated with NCI-H660 NEPC xenografts^[1].
FZ-AD005 (1-5 mg/kg; intravenous injection; once weekly; 2 total administrations) induces significant tumor growth inhibition in female BALB/c nude mice bearing NCI-H82 SCLC xenografts; at intravenous doses of 1, 3 and 5 mg/kg given once weekly for 2 total administrations, its TGI ranges from 76.52% to 97.13%^[1].
FZ-AD005 (1.5-6 mg/kg; intravenous injection; single administration) induces potent to complete tumor growth inhibition in mice bearing SCLC LU-5236 PDX, with TGIs ranging from 98.51% to 100.00% across different dose groups on day 21 post-administration^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

154128 (average)

Liquid

Colorless to light yellow

[FZ-AD005]

Shipping with dry ice.

-80°C, protect from light

• [1]. Guo Q, et al. FZ-AD005, a Novel DLL3-Targeted Antibody-Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models. Mol Cancer Ther. 2024;23(10):1367-1377.  [Content Brief]

  [2]. Liu J, et al. Unlocking New Horizons: Antibody–Drug Conjugates in Small Cell Lung Cancer[J]. Biology, 2025, 14(12): 1677.