Mipasetamab uzoptirine

Mipasetamab uzoptirine (ADCT-601) is an AXL-targeted antibody-drug conjugates (ADCs). Mipasetamab uzoptirine consists of a humanized anti-AXL antibody, a cleavable linker and the potent pyrrolobenzodiazepine (PBD) dimer cytotoxin SG3199. Mipasetamab uzoptirine can be used for the research of cancers[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> TAM Receptor

Mipasetamab uzoptirine 与可溶性和膜性 AXL 结合，被表达 AXL 的肿瘤细胞内化，从而释放 PBD 二聚体、导致 DNA 链间交联和随后的细胞杀伤[1]。 Mipasetamab uzoptirine 选择性抑制 AXL 阳性人类癌细胞 (Panc-1、A-172、SK-LU-1、MDA-MB-231、SK-OV-3、NCI-H1299、SN12C) 的生长 [1]. Mipasetamab uzoptirine (0 小时，4°C) 在 SN12C 细胞中表现出很强的细胞表面结合，并在 1 h 时与溶酶体共定位较好[1]。 Mipasetamab uzoptirine 增加 SN12C 细胞中的 DNA 链间交联水平[1]。 Cell Viability Assay[1] Cell Line: Panc-1, A-172, SK-LU-1, MDA-MB-231, SK-OV-3, NCI-H1299, and SN12C Concentration: 0-20 nM approximately Incubation Time: 5-8 days Result: Inhibited cell growth with IC50s of 0.47, 0.59, 0.02, 0.35, 0.11, 2.2, 0.83, 9.29, 14.62 nM respectively.

Mipasetamab uzoptirine (0.3-1 mg/kg，静脉注射) 抑制 MDA-MB-231 TNBC 异种移植和 SN12C 异种移植小鼠模型中的肿瘤生长[1]。 Mipasetamab uzoptirine (6 mg/kg，静脉注射) 在大鼠体内具有良好的耐受性并表现出出色的稳定性[1]。 Animal Model: SN12C xenograft mice model[1]. Dosage: 0.3-1 mg/kg Administration: i.v. Result: Inhibited tumor growth and increased survival rate.

[1]. Zammarchi F, et al. Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody-drug Conjugate Targeting AXL-expressing Cancers. Mol Cancer Ther. 2022 Apr 1;21(4):582-593.