TY - JOUR
T1 - Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer
AU - Huang, Peter Q.
AU - Boren, Brant C.
AU - Hegde, Sayee G.
AU - Liu, Hui
AU - Unni, Aditya K.
AU - Abraham, Sunny
AU - Hopkins, Chad D.
AU - Paliwal, Sunil
AU - Samatar, Ahmed A.
AU - Li, Jiali
AU - Bunker, Kevin D.
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/9/9
Y1 - 2021/9/9
N2 - Wee1 inhibition has received great attention in the past decade as a promising therapy for cancer treatment. Therefore, a potent and selective Wee1 inhibitor is highly desirable. Our efforts to make safer and more efficacious Wee1 inhibitors led to the discovery of compound 16, a highly selective Wee1 inhibitor with balanced potency, ADME, and pharmacokinetic properties. The chiral ethyl moiety of compound 16 provided an unexpected improvement of Wee1 potency. Compound 16, known as ZN-c3, showed excellent in vivo efficacy and is currently being evaluated in phase 2 clinical trials.
AB - Wee1 inhibition has received great attention in the past decade as a promising therapy for cancer treatment. Therefore, a potent and selective Wee1 inhibitor is highly desirable. Our efforts to make safer and more efficacious Wee1 inhibitors led to the discovery of compound 16, a highly selective Wee1 inhibitor with balanced potency, ADME, and pharmacokinetic properties. The chiral ethyl moiety of compound 16 provided an unexpected improvement of Wee1 potency. Compound 16, known as ZN-c3, showed excellent in vivo efficacy and is currently being evaluated in phase 2 clinical trials.
UR - https://www.scopus.com/pages/publications/85114397978
UR - https://www.scopus.com/pages/publications/85114397978#tab=citedBy
U2 - 10.1021/acs.jmedchem.1c01121
DO - 10.1021/acs.jmedchem.1c01121
M3 - Article
C2 - 34423975
AN - SCOPUS:85114397978
SN - 0022-2623
VL - 64
SP - 13004
EP - 13024
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 17
ER -
