Abstract
Many cancer diseases, e.g., prostate cancer and lung cancer, develop very slowly. Common chemotherapeutics like vincristine, vinblastine and taxol target cancer cells in their proliferating states. In slowly developing cancer diseases only a minor part of the malignant cells will be in a proliferative state, and consequently these drugs will exert a concomitant damage on rapidly proliferating benign tissue as well. A number of toxins possess an ability to kill cells in all states independently of whether they are benign or malignant. Such toxins can only be used as chemotherapeutics if they can be targeted selectively against the tumors. Examples of such toxins are mertansine, calicheamicins and thapsigargins, which all kill cells at low micromolar or nanomolar concentrations. Advanced prodrug concepts enabling targeting of these toxins to cancer tissue comprise antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT), lectin-directed enzyme-activated prodrug therapy (LEAPT), and antibody-drug conjugated therapy (ADC), which will be discussed in the present review. The review also includes recent examples of protease-targeting chimera (PROTAC) for knockdown of receptors essential for development of tumors. In addition, targeting of toxins relying on tumor-overexpressed enzymes with unique substrate specificity will be mentioned.
Highlights
Marialuigia Fantacuzzi and According to the International Union of Pure and Applied Chemistry (IUPAC), prodrugs are defined as chemically modified drugs that undergo biological and/or chemical transformation(s) before eliciting pharmacological responses [1]
A prodrug based on the overexpression of matrix metalloproteinases (MMPs) was designed for doxorubicin (Scheme 8) [34]
Was found to afafford a prodrug that was efficiently cleaved by prostate-specific antigen (PSA), and it showed a dramatically increased ford a prodrug that was efficiently cleaved by PSA, and it showed a dramatically inactivity activity in reducing xenografts in mice in as mice compared to that of creased in reducing xenografts as compared to native that ofdoxorubicin native dox(6)
Summary
Marialuigia Fantacuzzi and According to the International Union of Pure and Applied Chemistry (IUPAC), prodrugs are defined as chemically modified drugs that undergo biological and/or chemical transformation(s) before eliciting pharmacological responses [1]. Inactive compounds, which in the organism are modified into active drugs, are known as bio-precursor prodrugs Examples of such prodrugs are proguanil that in the liver is converted into the antimalarial drug cycloguanil [4], salicin that is converted into salicylic acid [5], and acetanilide that is converted into acetaminophen [3]. In the present review new developments in the fields of boronic acids as prodrugs, of anthracyclines, and of antibody–drug conjugates, targeting of paclitaxel and refined use of Alessandra Ammazzalorso. Molecules 2021, 26, 1292 anthracyclines, and of antibody–drug conjugates, targeting of paclitaxel and refined use of prostate-specific membrane antigen (PSMA) for delivery of payloads are described. A new problem of targeting oncogenes for neoplastic tissue in gene-directed enzyme prodrug group of prodrugs, which link two pharmacophores, i.e., PROtease.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
