Cyanine dye mediated mitochondrial targeting enhances the anti-cancer activity of small-molecule cargoes

The circadian rhythms are an intrinsic timekeeping system that regulates numerous physiological, biochemical, and behavioral processes at intervals of approximately 24 h. By regulating such processes, the circadian rhythm allows organisms to anticipate and adapt to continuously changing environmental conditions. A growing body of evidence shows that disruptions to the circadian rhythm can lead to various disorders, including cancer. Recently, crucial knowledge has arisen regarding the essential features that underlie the overt circadian rhythm and its influence on physiological outputs. This knowledge suggests that specific small molecules can be utilized to control the circadian rhythm. It has been discovered that these small molecules can regulate circadian-clock-related disorders such as metabolic, cardiovascular, inflammatory, as well as cancer. This review examines the potential use of small molecules for developing new drugs, with emphasis placed on recent progress that has been made regarding the identification of small-molecule clock modulators and their potential use in treating cancer.

Download Full-text

Kernels for small molecules and the prediction of mutagenicity, toxicity and anti-cancer activity

Bioinformatics ◽

10.1093/bioinformatics/bti1055 ◽

2005 ◽

Vol 21 (Suppl 1) ◽

pp. i359-i368 ◽

Cited By ~ 115

Author(s):

S. J. Swamidass ◽

J. Chen ◽

J. Bruand ◽

P. Phung ◽

L. Ralaivola ◽

...

Keyword(s):

Small Molecules ◽

Anti Cancer ◽

Cancer Activity

Download Full-text

Small molecule inhibitors of the mitochondrial ClpXP protease possess cytostatic potential and re-sensitize chemo-resistant cancers

Scientific Reports ◽

10.1038/s41598-021-90801-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Martina Meßner ◽

Melanie M. Mandl ◽

Mathias W. Hackl ◽

Till Reinhardt ◽

Maximilian A. Ardelt ◽

...

Keyword(s):

Small Molecules ◽

Small Molecule ◽

Small Molecule Inhibitors ◽

Breast Cancer Cell Lines ◽

Cancer Therapies ◽

Oxygen Species ◽

Transport Chain ◽

Anti Cancer ◽

Major Attention

AbstractThe human mitochondrial ClpXP protease complex (HsClpXP) has recently attracted major attention as a target for novel anti-cancer therapies. Despite its important role in disease progression, the cellular role of HsClpXP is poorly characterized and only few small molecule inhibitors have been reported. Herein, we screened previously established S. aureus ClpXP inhibitors against the related human protease complex and identified potent small molecules against human ClpXP. The hit compounds showed anti-cancer activity in a panoply of leukemia, liver and breast cancer cell lines. We found that the bacterial ClpXP inhibitor 334 impairs the electron transport chain (ETC), enhances the production of mitochondrial reactive oxygen species (mtROS) and thereby promotes protein carbonylation, aberrant proteostasis and apoptosis. In addition, 334 induces cell death in re-isolated patient-derived xenograft (PDX) leukemia cells, potentiates the effect of DNA-damaging cytostatics and re-sensitizes resistant cancers to chemotherapy in non-apoptotic doses.

Download Full-text

VER-155008, a small molecule inhibitor of HSP70 with potent anti-cancer activity on lung cancer cell lines

Experimental Biology and Medicine ◽

10.1177/1535370214527899 ◽

2014 ◽

Vol 239 (5) ◽

pp. 638-645 ◽

Cited By ~ 50

Author(s):

Wei Wen ◽

Wuxin Liu ◽

Yongfeng Shao ◽

Liang Chen

Keyword(s):

Lung Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Small Molecule ◽

Cancer Cell Lines ◽

Small Molecule Inhibitor ◽

Lung Cancer Cell ◽

Molecule Inhibitor ◽

Anti Cancer ◽

Cancer Activity

Download Full-text

Organometallic Small Molecule Kinase Inhibitors – Direct Incorporation of Re and 99mTc into Opaganib®

Chemical Communications ◽

10.1039/d1cc03678e ◽

2021 ◽

Author(s):

Roger Alberto ◽

Raphael Lengacher ◽

Youchao Wang ◽

Henrik Braband ◽

Olivier Blacque ◽

...

Keyword(s):

Cancer Cells ◽

Small Molecule ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Ic50 Value ◽

Anti Cancer ◽

Direct Incorporation ◽

Cancer Activity

[(η5-Cp)ReI(CO)3] was incorporated into the kinase inhibitor Opaganib®. The resulting bioorganometallic complex showed a similar anti-cancer activity to Opaganib® against PC-3 cancer cells. The IC50 value for the kinase SK2...

Download Full-text

Simple and Fast DNA Based Sensor System for Screening of Small-Molecule Compounds Targeting Eukaryotic Topoisomerase 1

Pharmaceutics ◽

10.3390/pharmaceutics13081255 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1255

Author(s):

Kamilla Vandsø Petersen ◽

Asier Selas ◽

Kirstine Mejlstrup Hymøller ◽

Karol Mizielinski ◽

Maria Thorsager ◽

...

Keyword(s):

Small Molecule ◽

Rolling Circle Amplification ◽

Amplification Product ◽

Rolling Circle ◽

Topoisomerase 1 ◽

Potential Target ◽

Enzyme Screening ◽

Anti Cancer ◽

The Individual ◽

Cancer Activity

Background: Eukaryotic topoisomerase 1 is a potential target of anti-parasitic and anti-cancer drugs. Parasites require topoisomerase 1 activity for survival and, consequently, compounds that inhibit topoisomerase 1 activity may be of interest. All effective topoisomerase 1 drugs with anti-cancer activity act by inhibiting the ligation reaction of the enzyme. Screening for topoisomerase 1 targeting drugs, therefore, should involve the possibility of dissecting which step of topoisomerase 1 activity is affected. Methods: Here we present a novel DNA-based assay that allows for screening of the effect of small-molecule compounds targeting the binding/cleavage or the ligation steps of topoisomerase 1 catalysis. This novel assay is based on the detection of a rolling circle amplification product generated from a DNA circle resulting from topoisomerase 1 activity. Results: We show that the binding/cleavage and ligation reactions of topoisomerase 1 can be investigated separately in the presented assay termed REEAD (C|L) and demonstrate that the assay can be used to investigate, which of the individual steps of topoisomerase 1 catalysis are affected by small-molecule compounds. The assay is gel-free and the results can be detected by a simple colorimetric readout method using silver-on-gold precipitation rendering large equipment unnecessary. Conclusion: REEAD (C|L) allows for easy and quantitative investigations of topoisomerase 1 targeting compounds and can be performed in non-specialized laboratories.

Download Full-text