Abstract
In this review, we have attempted to describe all of the antibody–drug conjugates using a marine-derived compound as the “warhead”, that are currently in clinical trials as listed in the current version of the NIH clinical trials database (clinicaltrials.gov). In searching this database, we used the beta-test version currently available, as it permitted more specific search parameters, since the regular version did not always find trials that had been completed in the past with some agents. We also added small discussion sections on candidates that are still at the preclinical stage, including a derivative of diazonamide that has an unusual interaction with tubulin (DZ-23840), which may also be a potential warhead in the future.
Highlights
At the time of writing this review, the following MMAE-linked Antibody Drug Conjugates (ADCs) are in clinical trials, but we should point out that in a few cases we have reported agents that have been in clinical trials, but whose current status is not too clear
We have attempted to fully update our earlier articles on this topic, and have given details on 31 ADCs that use the dolastatin derivatives originally described by the Pettit group and their collaborators
These include significant numbers based on auristatins MMAE or MMAF, together with related molecules that followed from the initial work on the MMAE/F by the Seattle
Summary
In early 2014, Newman and Cragg reviewed the status of antitumor and pain control agents whose base structures were related to or sourced from marine sources [1], which was followed by a more generalized short review requested for a Special Issue of Planta Medica published early in. What we have decided to do is to report the ADCs sorted by their “warhead” without taking into account, the class of linker between the “warhead” and the mAb. In addition, if there are subtle changes in the warhead from a known structure, we will discuss these and show what may be a candidate for other mAbs in the future. If there are subtle changes in the warhead from a known structure, we will discuss these and show what may be a candidate for other mAbs in the future We realize that this is not a “complete” account, as at times, reports are made in the literature using only a code name for an ADC and no information as to the “warhead”. This review is as complete as we can make it using publicly available resources, but it will not contain every marine-derived warhead extant
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