Choi, PJ, Tomek, P, Tercel, M, Reynisson, J ORCID:, Park, TIH, Cooper, EA, Denny, WA, Jose, J and Leung, E (2022) Conjugation of Palbociclib with MHI-148 Has an Increased Cytotoxic Effect for Breast Cancer Cells and an Altered Mechanism of Action. Molecules, 27 (3). pp. 1-14.

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The CDK4/6 inhibitor palbociclib, combined with endocrine therapy, has been shown to be effective in postmenopausal women with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer. However, palbociclib is not as effective in the highly aggressive, triple-negative breast cancer that lacks sensitivity to chemotherapy or endocrine therapy. We hypothesized that conjugation of the near-infrared dye MHI-148 with palbociclib can produce a potential theranostic in triple-negative, as well as estrogen receptor-positive, breast cancer cells. In our study, the conjugate was found to have enhanced activity in all mammalian cell lines tested in vitro. However, the conjugate was cytotoxic and did not induce G1 cell cycle arrest in breast cancer cells, suggesting its mechanism of action differs from the parent compound palbociclib. The study highlights the importance of investigating the mechanism of conjugates of near-infrared dyes to therapeutic compounds, as conjugation can potentially result in a change of mechanism or target, with an enhanced cytotoxic effect in this case.

Item Type: Article
Additional Information: © 2022 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 (
Uncontrolled Keywords: CDK4; 6 inhibitor palbociclib; near-infrared fluorescent (NIRF); MHI-148; breast cancer; cell cycle arrest
Subjects: R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RM Therapeutics. Pharmacology > Physical medicine. Physical therapy. Including massage, exercise, occupational therapy, hydrotherapy, phototherapy, radiotherapy, thermotherapy, electrotherapy
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Related URLs:
Depositing User: Symplectic
Date Deposited: 04 Mar 2022 08:39
Last Modified: 13 Apr 2022 12:24

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