Disitamab Vedotin Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Disitamab Vedotin is mainly used to treat patients with locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) with HER2 overexpression who have received at least two systemic chemotherapy regimens. It was first approved in China, providing a new treatment option for patients with HER2-positive gastric cancer who are resistant or intolerant to existing treatment options.
Mechanism of action
Disitamab Vedotin is an antibody-drug conjugate (ADC) consisting of the human epidermal growth factor receptor 2 (HER2)-specific antibody hertuzumab (disitamab) connected to the cytotoxic monomer monomethyl auristatin E (MMAE) through a cleavable valine-citrulline-para-aminobenzoic acid alanine carbonate (mc-Val-Cit-PABC) linker. This design enables disitamab vedotin to specifically target HER2-overexpressing cancer cells and release MMAE after entering the cells through internalization, inducing cell apoptosis.
Synthese
Disitamab Vedotin is produced by conjugating the antibody hertuzumab to mc-Val-Cit-PABC-MMAE (29.3). General methods for such conjugation have been provided in the patent literature and begin with the partial reduction of the disulfide bonds present in the hertuzumab antibody. This is accomplished by treating the antibody with tris(2-carboxyethyl)phosphine (TCEP) and bisethylenediaminepentaacetic acid (DTPA) in phosphate buffered saline (PBS) to produce 29.2. The sulfhydryl groups present in 29.2 react with a dimethyl sulfoxide (DMSO) solution of 29.3 to obtain Disitamab Vedotin.
Disitamab Vedotin Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
