Some Findings About IMMU-132!

2019 was a very exciting year with three ADC drugs approved by FDA, followed by one more new ADC, Sacituzumab Govitecan (IMMU-132) approved in 2020 from Immunomedics.

IMMU-132, also known as Trodelvy, is an immune targeted therapy medicine for triple-negative breast cancer. The drug consists of sacituzumab and SN-38 with a linker in between. Sacituzumab is an mAb that targets the Trop-2 protein, which is found in over 90% of triple-negative breast cancers. SN-38 is an inhibitor carried by sacituzumab that targets the designated area, which makes it more effective in treating cancer cells and less toxic to healthy cells.

In the scheme below, azido-PEG8-amine is reacted with 1,4-dioxane-2,6-dione, followed by coupling with MMT-protected-Lys-benzyl-alcohol to generate Azido-PEG-Lys-benzyl alcohol. Further reaction with SN-38 is followed by Click Chemistry with 4-(N-maleimidomethyl)-N-(2-propynyl)cyclohexane-1-carboxamide to produce Mal-PEG-Lys-PAB-SN38, which is then incubated with sacituzumab, a monoclonal antibody, to produce IMMU-132.

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