Soblidotin (TZT-1027) (Auristatin PE) is an inhibitor of tubulin polymerization. It is also a novel synthetic Dolastatin 10 derivative.

Soblidotin (Auristatin PE) inhibits the growth of several tumoral cell lines and induces caspase-3-dependent apoptosis. Soblidotin (Auristatin PE) also shows antitumoral activity in Vincristine-, Docetaxel-, and Paclitaxel-resistant tumors, which makes it a potential chemotherapy drug for use in tumors that do not respond to other microtubule inhibitors [2]. Soblidotin (Auristatin PE) exhibits antitumor activity against p-glycoprotein-overexpressing cell lines established from colon cancer H116 and breast cancer-resistant protein-positive cell lines established from lung cancer PC-6 and is more potent than Vincristine, Paclitaxel, and Docetaxel against these cell lines [1].

Auristatin PE (Soblidotin/TZT-1027) demonstrates significant antitumor and antivascular activities across various models. In cancer models, especially those with high VEGF expression and murine colon tumors, it increases vascular permeability, induces vessel closure, and causes extensive hemorrhage. When administered intravenously, Auristatin PE effectively inhibits the growth of P388 leukemic cells and solid tumors in mice, extending survival rates. Its efficacy is on par with or exceeds that of established chemotherapy agents such as Dolastatin 10, Cisplatin, Vincristine, and 5-Fluorouracil. It does not affect the PD184352-mediated inhibition of ERK1/2 phosphorylation, indicating a distinct mechanism of action. Additionally, after administration, it significantly reduces intratumoral blood flow, leading to hemorrhagic necrosis. In HT-29 tumor-bearing mice, a schedule of once every seven days at dosages of 0.5 or 1.0 mg/kg over four cycles effectively inhibits tumor growth in a dose-dependent manner. This effect is corroborated by a decrease in Ki-67 positive proliferating cells and an increase in TUNEL-positive cells, indicating enhanced cell death, particularly when combined with PD184352, within 24 hours post-treatment.