Rago, Brian published the artcileQuantitative Conjugated Payload Measurement Using Enzymatic Release of Antibody-Drug Conjugate with Cleavable Linker, Related Products of amides-buliding-blocks, the publication is Bioconjugate Chemistry (2017), 28(2), 620-626, database is CAplus and MEDLINE.
As antibody-drug conjugate (ADC) design is evolving with novel payload, linker, and conjugation chem., the need for sensitive and precise quant. measurement of conjugated payload to support pharmacokinetics (PK) is in high demand. Compared to ADCs containing noncleavable linkers, a strategy specific to linkers which are liable to pH, chem. reduction, or enzymic cleavage has gained popularity in recent years. One bioanal. approach to take advantage of this type of linker design is the development of a PK assay measuring released conjugated payload. For the ADC utilizing a dipeptide ValCit linker studied in this report, the release of payload PF-06380101 was achieved with high efficiency using a purified cathepsin B enzyme. The subsequent liquid chromatog. mass spectrometry (LC/MS) quantitation leads to the PK profile of the conjugated payload. For this particular linker using a maleimide-based conjugation chem., one potential route of payload loss would result in an albumin adduct of the linker-payload. While this adduct’s formation has been previously reported, here, for the first time, we have shown that payload from a source other than ADC contributes only up to 4% of total conjugated payload while it accounts for approx. 35% of payload lost from the ADC at 48 h after dosing to rats.
Bioconjugate Chemistry published new progress about 916746-27-5. 916746-27-5 belongs to amides-buliding-blocks, auxiliary class ADC Linker,Enzymatic Cleavage Linker, name is (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, and the molecular formula is C21H33N5O7, Related Products of amides-buliding-blocks.
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