2024年3月22日 · Here, we introduce a unique next generation ADC platform based on Sortase-mediated antibody conjugation (SMAC-Technology) yielding in very homogenous and stable drug conjugates with limited systemic, but powerful anti-tumor activity. The highly potent payload used is a proprietary derivative of the Anthracycline PNU-159682.

Here, we introduce a unique next-generation ADC platform based on Sortase-mediated antibody conjugation (SMAC-TechnologyTM), yielding in very homogenous and stable drug conjugates with limited systemic, but powerful anti-tumor activity. The highly potent payload used is PNU-EDA, a proprietary derivative of the anthracycline PNU-159682.

2020年12月15日 · PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker dr …

蒽环类药物如阿霉素（doxorubicin）是目前骨肉瘤的一线化疗药物之一，能插入DNA双螺旋中，阻止双链分离，影响DNA复制和RNA合成。 阿霉素作为ADC有效载荷由于细胞毒性不够（doxorubicin的IC50见图2），开发了另一种细胞毒性比阿霉素高100倍的蒽环类药 …

PNU-159682 是蒽环类新霉素的代谢产物，是一种 DNA 拓扑异构酶 II (Topo II) 抑制剂，具有出色的细胞毒性。 在ADC 合成中，PNU-159682 是一种比阿霉素更有效和耐受性更高的 ADC 细胞毒素 (ADC cytotoxin)。

The PNU anthracycline payload is about 3 logs more potent than tubulin-targeting ADC payloads, and thus requires a highly stable linker to covalently attach it to the antibody. Using NBE-Therapeutics' SMAC-Technology TM, best-in-class serum stability is achieved, while at the same time maintaining high potency of ADCs with this toxin.

2023年5月17日 · These findings suggest that identification of HIO-refractory antibodies to be used in ADC format may improve therapeutic efficacy as observed by NAV-001 and warrants NAV-001-PNU’s advancement to human clinical trials as a monotherapy to …

2020年12月15日 · Herein we seek to evaluate PNU-159682 for use in an ADC platform. Medicinal chemistry was utilized to assess structure activity relationships around both the C-14 alcohol side chain and, to a lesser extent, around the saturated tricyclic heterocycle.

2020年，一种基于PNU-159682的新型ADC 药物NBE-002，靶向ROR1，进入了I/II期临床试验 (NCT04441099)。 另外，NBE-002还诱导了长期的免疫保护，这使得它可以成功地与免疫检查点抑制剂组合治疗。

2024年12月10日 · As an ADC payload, adriamycin lacks sufficient cytotoxicity (IC 50 shown in Figure 2), prompting the development of PNU-159682, which exhibits 100 times greater cytotoxicity. PNU-159682, a liver metabolite of nemorubicin, inhibits DNA topoisomerase II and is three orders of magnitude more potent, with an IC 50 of 20-100 picomolar.