TY - JOUR
T1 - Antineoplastic Agents. 604. the Path of Quinstatin Derivatives to Antibody Drug Conjugates
AU - Pettit, George
AU - Melody, Noeleen
AU - Chapuis, Jean
N1 - Funding Information:
With appreciation, we acknowledge and thank for financial support the Arizona Biomedical Research Commission, the J.W. Kiecknefer Foundation, and the Margaret T. Morris Foundation. In addition, we are pleased to thank Drs. K. Gish, A. Haight, and X. Shen for useful discussions.
Publisher Copyright:
© 2017 The American Chemical Society and American Society of Pharmacognosy.
PY - 2017/9/22
Y1 - 2017/9/22
N2 - To further evaluate the exceptional cancer cell growth inhibition by the quinstatins, of which one of the series, quinstatin 8, approaches the exceptional cytotoxic activity of the parent dolastatin 10 (1), four of the quinstatins have been converted to desmethyl derivatives. Three of the four (4, 5, and 8 [7b-d]) were next bonded to the linker (8) employed in the synthesis of the very successful and structurally related anticancer drug Adcetris (3). Owing to these structural modifications, a next step could be taken by bonding to a monoclonal antibody, thereby producing an antibody drug conjugate (ADC) related to Adcetris structurally but with the possibility of a wider spectrum of activity and utility.
AB - To further evaluate the exceptional cancer cell growth inhibition by the quinstatins, of which one of the series, quinstatin 8, approaches the exceptional cytotoxic activity of the parent dolastatin 10 (1), four of the quinstatins have been converted to desmethyl derivatives. Three of the four (4, 5, and 8 [7b-d]) were next bonded to the linker (8) employed in the synthesis of the very successful and structurally related anticancer drug Adcetris (3). Owing to these structural modifications, a next step could be taken by bonding to a monoclonal antibody, thereby producing an antibody drug conjugate (ADC) related to Adcetris structurally but with the possibility of a wider spectrum of activity and utility.
UR - http://www.scopus.com/inward/record.url?scp=85029774018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029774018&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.7b00237
DO - 10.1021/acs.jnatprod.7b00237
M3 - Article
C2 - 28895394
AN - SCOPUS:85029774018
SN - 0163-3864
VL - 80
SP - 2447
EP - 2452
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 9
ER -