Apoptosis inducer (BCL XL inhibitor) Overexpression of anti apoptotic Bcl-2 family members (including BCL XL) is one of the mechanisms for cancer cells to obtain apoptosis resistance. Drugs that block the BH3 binding domain on BCL XL can trigger cancer cell apoptosis. Telanstadine and its analogues Targeted spliceosome is a large ribonucleoprotein complex involved in […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Pyrrole benzodiazepines and indole chlorobenzodiazepines Pyrrolo [2,1-c] [1,4] benzodiazepine (PBD) is a natural product with antitumor activity. Their mode of action is selective alkylation in small grooves of DNA, in which the N2 of guanine forms a covalent bond with the electrophilic […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Calendula Auristatins is an important payload used in ADC. The most famous family member MMAE exists in two listed drugs, adcetris and Polivy. At present, more than 10 kinds of ADCs with calendula (such as MMAE) or methylcalendula f (MMAF) […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Microtubule destroying drug 1. Calendula Auristatins is an important payload used in ADC. The most famous family member MMAE exists in two listed drugs, adcetris and Polivy. At present, more than 10 kinds of ADCs with calendula (such as MMAE) or methylcalendula […]
Table2. Chemical triggers Conjugate linker is not only the molecular part forming covalent connection between antibody and small molecule payload, but also the key element with design properties in targeted drug therapy. The addition of linkers should not induce aggregation, and it is necessary to ensure acceptable PK characteristics, limit the premature release (stability) of […]
1. Mylotarg® (gemtuzumab ozogamicin) from Wyeth/Pfizer was the first ADC to reach the market. It is composed of a recombinant humanized anti-CD33 mAb (IgG4κ antibody hP67.6) covalently attached to a calicheamicin derived payload (N-acetyl-γ-calicheamicin 1,2-dimethyl hydrazine dichloride) via a pH-sensitive hydrazone linker. 2. Adcetris® (brentuximab vedotin) from Seagen (formerly Seattle Genetics), containing a CD30-specific mAb conjugated to […]
FDA approved Antibody-drug conjugate (ADC) for clinical use Clinically, most of the ADC drugs approved by FDA are IgG1, and the targets are CD33, CD22, HER2 and so on. The most common payload is MMAE, also contains calicheamicin, DM1. ADC drugs are mainly used in the field of antitumor, which is one of the hot […]
The structure of antibody-drug conjugate (ADC) ADC consists of antibodies and payload, linker connects antibodies and small molecule drugs. After ADC drugs enter the blood, its antibody part will recognize and bind to the surface antigen of target cells. Theninternalizing ADC antigen complex into cells through endocytosis, the complex will be degraded by lysosomes and […]
Since 1975, monoclonal antibodies have been successfully used for the diagnosis and therapeutics. In 1993, heavy-chain-only antibodies which bind to antigens was discovered in camelids. The variable domain of heavy chain antibody (VHH) was called as nanobodies and it was anticipated as the better therapeutic antibodies in future due to its high stability, refoldability, and manipulable characteristics. […]
Controlled Fab arm exchange (cFAE) has proven to be a generic and versatile technology for the efficient generation of IgG-like bispecific antibodies (DuoBodies or DBs). This involves the recombination of antigen-binding arms (heavy chain–light chain (H-L) pairs) between individually expressed antibody molecules and is termed Fab-arm exchange, can be modified to make the routine generation […]
