Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer

Peter Q. Huang; Brant C. Boren; Sayee G. Hegde; Hui Liu; Aditya K. Unni; Sunny Abraham; Chad D. Hopkins; Sunil Paliwal; Ahmed A. Samatar; Jiali Li; Kevin D. Bunker

doi:10.1021/acs.jmedchem.1c01121

Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer

Peter Q. Huang
, Brant C. Boren
, Sayee G. Hegde
, Hui Liu
, Aditya K. Unni
, Sunny Abraham
, Chad D. Hopkins
, Sunil Paliwal
, Ahmed A. Samatar
, Jiali Li
, Kevin D. Bunker

Department of Chemistry and Chemical Biology

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	13004-13024
Number of pages	21
Journal	Journal of Medicinal Chemistry
Volume	64
Issue number	17
DOIs	https://doi.org/10.1021/acs.jmedchem.1c01121
State	Published - 9 Sep 2021

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10.1021/acs.jmedchem.1c01121

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Huang, P. Q., Boren, B. C., Hegde, S. G., Liu, H., Unni, A. K., Abraham, S., Hopkins, C. D., Paliwal, S., Samatar, A. A., Li, J., & Bunker, K. D. (2021). Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer. Journal of Medicinal Chemistry, 64(17), 13004-13024. https://doi.org/10.1021/acs.jmedchem.1c01121

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title = "Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer",

abstract = "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.",

author = "Huang, \{Peter Q.\} and Boren, \{Brant C.\} and Hegde, \{Sayee G.\} and Hui Liu and Unni, \{Aditya K.\} and Sunny Abraham and Hopkins, \{Chad D.\} and Sunil Paliwal and Samatar, \{Ahmed A.\} and Jiali Li and Bunker, \{Kevin D.\}",

note = "Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

month = sep,

day = "9",

doi = "10.1021/acs.jmedchem.1c01121",

language = "English",

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Huang, PQ, Boren, BC, Hegde, SG, Liu, H, Unni, AK, Abraham, S, Hopkins, CD, Paliwal, S, Samatar, AA, Li, J & Bunker, KD 2021, 'Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer', Journal of Medicinal Chemistry, vol. 64, no. 17, pp. 13004-13024. https://doi.org/10.1021/acs.jmedchem.1c01121

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.

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

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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 -

Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer

Abstract

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