Lupartumab Amadotin

Lupartumab Amadotin (BAY 1129980) is an antibody–drug conjugate (ADC) consisting of a fully human C4.4A (LYPD3)-targeting mAb (BAY 1135626; HY-147281) conjugated to a novel, highly potent derivative of the microtubule-disrupting cytotoxic drug auristatin via a noncleavable alkyl hydrazide linker. Lupartumab Amadotin can be used for the research of non-small cell lung cancer[1].

Research Areas >> Cancer

human C4.4A[1]

Lupartumab Amadotin (BAY 1129980; 0-2 nM; 72 h) 在内源性表达 C4.4A 的细胞系中显示出强大的抗增殖功效，并抑制 C4.4A 转染的 A549 肺癌细胞的增殖，与非靶向对照 ADC 相比显示出选择性[1]。 Cell Viability Assay[1] Cell Line: hC4.4A:A549, mock:A549, NCI-H292, FaDu, NCI-H322, SCaBER and SCC-4 cells Concentration: 0-2 nM Incubation Time: 72 h Result: High potency at subnanomolar range (IC50=0.05 nM) was observed in hC4.4A:A549 lung cancer cells, a remarkable selectivity (over 1,000-fold) compared with mock:A549 cells was observed. Showed high potency with IC50s at single- to double-digit nanomolar range and even at subnanomolar range (IC50 of 0.6 nM) in NCI-H292 lung cancer cell line.

Lupartumab Amadotin (BAY 1129980; 1.9-15 mg/kg; i.v.; Q4D×3) 在 C4.4A 阳性的 NCI-H292 和 NCI-H322 NSCLC 异种移植模型中显示出抗肿瘤效果[1]。 Lupartumab Amadotin (BAY 1129980; 7.5 and 15 mg/kg; i.v.; Q4D×3) 显示在 NSCLC 患者源性异种移植 (PDX) 模型中 C4.4A 靶点依赖的抗肿瘤疗效[1]。 Animal Model: NMRI nu/nu mice, C4.4A-positive NCI-H292 human NSCLC xenograft model[1] Dosage: 1.9, 3.75, 7.5 and 15 mg/kg Administration: IV, Q4D×3 Result: Halted tumor growth dose dependently with a minimum effective dose (MED) of 1.9 mg/kg. The first treatment cycle with 15 mg/kg drug (Q4D×3) resulted in a marked delay of tumor growth with a significantly reduced tumor volume, as compared to vehicle, Cisplatin (HY-17394), or control ADC.

[1]. Willuda J, et al. Preclinical Antitumor Efficacy of BAY 1129980-a Novel Auristatin-Based Anti-C4.4A (LYPD3) Antibody-Drug Conjugate for the Treatment of Non-Small Cell Lung Cancer. Mol Cancer Ther. 2017 May;16(5):893-904.