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Novel Non-Congeneric Derivatives of the Choline Kinase Alpha Inhibitor ICL-CCIC-0019

Wang, Ning; Brickute, Diana; Braga, Marta; Barnes, Chris; Lu, Haonan; Allott, Louis; Aboagye, Eric O.


Ning Wang

Diana Brickute

Marta Braga

Chris Barnes

Haonan Lu

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Dr Louis Allott
Lecturer in Translational Radiopharmaceutics

Eric O. Aboagye


Choline kinase alpha (CHKA) is a promising target for the development of cancer therapeutics. We have previously reported ICL-CCIC-0019, a potent CHKA inhibitor with high cellular activity but with some unfavorable pharmacological properties. In this work, we present an active analogue of ICL-CCIC-0019 bearing a piperazine handle (CK146) to facilitate further structural elaboration of the pharmacophore and thus improve the biological profile. Two different strategies were evaluated in this study: (1) a prodrug approach whereby selective CHKA inhibition could be achieved through modulating the activity of CK146, via the incorporation of an ε-(Ac) Lys motif, cleavable by elevated levels of histone deacetylase (HDAC) and cathepsin L (CTSL) in tumour cells; (2) a prostate-specific membrane antigen (PSMA) receptor targeted delivery strategy. Prodrug (CK145) and PSMA-targeted (CK147) derivatives were successfully synthesized and evaluated in vitro. While the exploitation of CK146 in those two strategies did not deliver the expected results, important and informative structure-activity relationships were observed and have been reported.


Wang, N., Brickute, D., Braga, M., Barnes, C., Lu, H., Allott, L., & Aboagye, E. O. (2021). Novel Non-Congeneric Derivatives of the Choline Kinase Alpha Inhibitor ICL-CCIC-0019. Pharmaceutics, 13(7), Article 1078.

Journal Article Type Article
Acceptance Date Jul 9, 2021
Online Publication Date Jul 14, 2021
Publication Date 2021-07
Deposit Date Jul 28, 2021
Publicly Available Date Oct 27, 2022
Journal Pharmaceutics
Print ISSN 1999-4923
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 13
Issue 7
Article Number 1078
Keywords Choline kinase alpha (CHKA) inhibitor; ICL-CCIC-0019; Prodrug; PSMA; Targeted drug delivery; PIK4CB
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Copyright Statement
Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).

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