Becotatug vedotin

Members of the human epidermal growth factor receptor (HER) family, which includes HER1 (also known as EGFR), HER2, HER3 and HER4, have played a central role in regulating cell proliferation, survival, differentiation and migration. The overexpression of the HER family has been recognized as one of the most common cellular dysregulation associated with a wide variety of tumor types. Antibody-drug conjugates (ADCs) represent a new and promising class of anticancer therapeutics that combine the cancer specificity of antibodies with cytotoxicity of chemotherapeutic drugs. Two HER2-directed ADCs, trastuzumane-emtansine (T-DM1) and trastuzumab-deruxtecan (DS-8201a), have been approved for HER2-positive metastatic breast cancer by the U.S. Food and Drug Administration (FDA) in 2013 and 2019, respectively. A third HER2-directed ADC, disitamab vedotin (RC48), has been approved for locally advanced or metastatic gastric or gastroesophageal junction cancer by the NMPA (National Medical Products Administration) of China in 2021. A total of 11 ADCs that target HER family receptors (EGFR, HER2 or HER3) are currently under clinical trials. In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges.

Recently, magnetorheological grease (MRG) has been utilized in magnetorheological (MR) brakes to generate a braking torque based on the current applied. However, the high initial viscosity of MRG has increased the off-state torque that led to the viscous drag of the brake. Therefore, in this study, the off-state viscosity of MRG can be reduced by the introduction of dilution oil as an additive. Three samples consist of pure MRG (MRG 1) and MRG with different types of dilution oil; hydraulic (MRG 2) and kerosene (MRG 3) were prepared by mixing grease and spherical carbonyl iron particles (CIP) using a mechanical stirrer. The rheological properties in the rotational mode were examined using a rheometer and the torque performances in MR brake were evaluated by changing the current of 0 A, 0.4 A, 0.8 A, and 1.2 A with fixed angular speed. The result shows that MRG 3 has the lowest viscosity which is almost 93% reduction while the viscosity of MRG 2 has lowered to 25%. However, the torque performances generated by MRG 3 were highest, 1.44 Nm, when 1.2 A of current was applied and followed by MRG 2 and MRG 1. This phenomenon indicated that the improvement of torque performances was dependent on the viscosity of MRG. By reducing the viscosity of MRG, the restriction on CIP to form chain formation has also decreased and strengthen the torque of MRG brake. Consequently, the utilization of dilution oil in MRG could be considered in MR brake in near future.