What is an ADC Payload?

What is an ADC Payload?

Published by BroadPharm on April 03, 2024

ADC payloads are a class of cytotoxic molecules that are conjugated to mAb (antibody) for oncology and other therapeutic treatment. The payload in the conjugate (ADC) will be released inside cells either through mechanisms of enzyme digestion, low pH, or reduction condition, etc.

There are totally 15 ADC drugs approved up to 2023, of which 13 ADCs are currently on market.

The payloads in approved ADC drugs are classified into three major classes, tubulin binder (inhibitor), DNA targeting (DNA damaging) and topoisomerase I inhibitor.

Tubulin inhibitors used in ADCs are exemplified by MMAE, MMAF, and DM1 (see Table 1).

DNA targeting agents used in ADCs are represented by PBD, Calicheamicin (see Table 1).

Topoisomerase I inhibitors used in ADCs are represented by SN-38, DXD (see Table 1).

ADC is currently a very dynamic field with more than 33 drugs in phase 2 and 3 clinical trial and more in early-stage phase 1 and 2 trial. The distribution of the various payloads used in ADCs is depicted in Figure. 1.

As a leading supplier of ADC payloads and ADC linkers worldwide, BroadPharm provides a variety of payload compounds including tubulin inhibitors, DNA targeting agents, and topoisomerase I inhibitors to empower our clients' advanced drug discovery and development.

Table. 1. Payloads in Approved ADC Drugs

Payload Class Payload Name Approved Drug Name Payload Structure
Tubulin binders MMAE Disitamab vedotin
MMAE Brentuximab vedotin
MMAE Polatuzumab vedotin
MMAE Enfortumab vedotin
MMAE Tisotumab vedotin
MMAF Belantamab mafodotin
DM1 Trastuzumab emtansine
DM4 Mirvetuximab soravtansine
DNA-targeting Calicheamicin Gemtuzumab ozogamicin
Calicheamicin Inotuzumab ozogamicin
PBD Loncastuximab tesirine
Top I inhibitors DX-8951 Trastuzumab deruxtecan
SN-38 Sacituzumab govitecan
Protein synthesis inhibitor PE38 Moxetumomab pasudotox A truncated form of Pseudomonas exotoxin (PE38) (MW~71,000)
Photosensitizer IR700 Cetuximab saratolacan

Figure. 1. Distribution of Payloads used in ADCs.