التفاصيل البيبلوغرافية
| العنوان: |
Novel Non-Congeneric Derivatives of the Choline Kinase Alpha Inhibitor ICL-CCIC-0019 |
| المؤلفون: |
Ning Wang, Diana Brickute, Marta Braga, Chris Barnes, Haonan Lu, Louis Allott, Eric O. Aboagye |
| المصدر: |
Pharmaceutics; Volume 13; Issue 7; Pages: 1078 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
choline kinase alpha (CHKA) inhibitor, ICL-CCIC-0019, prodrug, PSMA, targeted drug delivery, PIK4CB |
| الوصف: |
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. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Biologics and Biosimilars; https://dx.doi.org/10.3390/pharmaceutics13071078 |
| DOI: |
10.3390/pharmaceutics13071078 |
| الاتاحة: |
https://doi.org/10.3390/pharmaceutics13071078 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.8BAE2FCE |
| قاعدة البيانات: |
BASE |