10.1021/acsmedchemlett.6b00274.s001
Carolyn A. Leverett
Carolyn A.
Leverett
Sai Chetan K. Sukuru
Sai
Chetan K. Sukuru
Beth C. Vetelino
Beth C.
Vetelino
Sylvia Musto
Sylvia
Musto
Kevin Parris
Kevin
Parris
Jayvardhan Pandit
Jayvardhan
Pandit
Frank Loganzo
Frank
Loganzo
Alison
H. Varghese
Alison
H.
Varghese
Guoyun Bai
Guoyun
Bai
Bin Liu
Bin
Liu
Dingguo Liu
Dingguo
Liu
Sarah Hudson
Sarah
Hudson
Venkata Ramana Doppalapudi
Venkata Ramana
Doppalapudi
Joseph Stock
Joseph
Stock
Christopher J. O’Donnell
Christopher J.
O’Donnell
Chakrapani Subramanyam
Chakrapani
Subramanyam
Design, Synthesis, and Cytotoxic Evaluation of Novel
Tubulysin Analogues as ADC Payloads
American Chemical Society
2016
cancer cell lines
C -11 acetate functionality
SMDC
cytotoxic tubulysin analogues
Cytotoxic Evaluation
ADC Payloads
novel tubulysin analogues
multidrug-resistant carcinoma models
chemistry community
tubulysin-based ADCs
Novel Tubulysin Analogues
site-specific conjugation
molecule drug conjugates
chemistry approach
vivo stability
tubulysin class
2016-08-26 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Design_Synthesis_and_Cytotoxic_Evaluation_of_Novel_Tubulysin_Analogues_as_ADC_Payloads/3810699
The
tubulysin class of natural products has attracted much attention
from the medicinal chemistry community due to its potent cytotoxicity
against a wide range of human cancer cell lines, including significant
activity in multidrug-resistant carcinoma models. As a result of their
potency, the tubulysins have become an important tool for use in targeted
therapy, being widely pursued as payloads in the development of novel
small molecule drug conjugates (SMDCs) and antibody–drug conjugates
(ADCs). A structure-based and parallel medicinal chemistry approach
was applied to the synthesis of novel tubulysin analogues. These efforts
led to the discovery of a number of novel and potent cytotoxic tubulysin
analogues, providing a framework for our simultaneous report, which
highlights the discovery of tubulysin-based ADCs, including use of
site-specific conjugation to address in vivo stability of the C-11
acetate functionality.