Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies

Tarpley, Michael; Oladapo, Helen; Strepay, Dillon; Caligan, Thomas B.; Chdid, Lhoucine; Shehata, Hassan; Roques, Jose; Thomas, Rhashad; Laudeman, Christopher P.; Onyenwoke, Rob U.; Darr, David B.; Williams, Kevin P.

doi:10.1016/j.ejps.2021.105821

Cited by 28 publications

(23 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… The data presented in this article support the accompanying research article “Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies” [1] . As DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1a) plays a role in the pathophysiology of a number of diseases including diabetes, cancer and neurodegeneration [2] , [3] , [4] , the identification of DYRK1A inhibitors is of significant interest.…”

supporting

confidence: 68%

“…Sci. 162 (2021) 105821. doi: 10.1016/j.ejps.2021.105821) [1] . Table 1 lists a dataset for all 22 hits (Prestwick ID, chemical structure and name) from a pilot high-throughput screen of a library of approved compounds versus the kinase DYRK1A and lists those compounds having percent inhibition values >50%, including harmine and 4 of its analogs (harmol, harmaline, harmane and harmalol).…”

Section: Data Descriptionmentioning

confidence: 99%

“…3 also includes representative images for these data. Cell data on harmine and harmol are primarily included in [1] . The raw data are deposited at https://doi.org/10.17632/3r9r4s5yvm.1 .…”

Section: Data Descriptionmentioning

confidence: 99%

“…(E) Representative high-content images for harmine and harmol (33.3 and 66.7 µM) on H4 (upper panel) and U87 (lower panel) glioma cells. Images for 16.7 μM are included in the accompanying article [1] . …”

Section: Data Descriptionmentioning

confidence: 99%

See 3 more Smart Citations

Data supporting a pilot high-throughput screen of a drug library for identification of DYRK1A inhibitors and high-content imaging analysis of identified harmine analogs

et al. 2021

Self Cite

View full text Add to dashboard Cite

The data presented in this article support the accompanying research article “Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies” [1] . As DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1a) plays a role in the pathophysiology of a number of diseases including diabetes, cancer and neurodegeneration [2] , [3] , [4] , the identification of DYRK1A inhibitors is of significant interest. This data article details the hits identified from a DYRK1A high-throughput screen of a small molecule compound library containing over 95% approved drugs. Twenty-two compounds were identified with >50% inhibition, including harmine and four of its analogs. Subsequent profiling of these harmine analogs using glioma cancer cell lines and high-content image analysis identified those with effects on growth and cytotoxicity.

show abstract

supporting

confidence: 68%

Section: Data Descriptionmentioning

confidence: 99%

“…3 also includes representative images for these data. Cell data on harmine and harmol are primarily included in [1] . The raw data are deposited at https://doi.org/10.17632/3r9r4s5yvm.1 .…”

Section: Data Descriptionmentioning

confidence: 99%

Section: Data Descriptionmentioning

confidence: 99%

See 2 more Smart Citations

Data supporting a pilot high-throughput screen of a drug library for identification of DYRK1A inhibitors and high-content imaging analysis of identified harmine analogs

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…It may also promote the survival of malignant cells by inhibiting pro-apoptotic pathways since the loss of DYRK1A can activate p53 (the increased degradation of DYRK1A caused by p53 activation is mediated by MDM2, which was found to interact with and ubiquitinate DYRK1A, ultimately leading to its proteasomal degradation) [191,192]. DYRK1A likely plays a tumor type-specific role, so whether DYRK1A inhibition would promote or inhibit tumor cell growth depends on the tissue type and tumor microenvironment.Although DYRK1A is most widely characterized for its role in brain development, DYRK1A is overexpressed in various diseases, including many types of cancers, such as leukemia [193,194], pancreatic adenocarcinoma [195][196][197], and gliomas [198,199].…”

Section: Cancermentioning

confidence: 99%

Diabetic Kinome Inhibitors—A New Opportunity for β-Cells Restoration

Pucelik

Barzowska

Dąbrowski

et al. 2021

IJMS

View full text Add to dashboard Cite

Diabetes, and several diseases related to diabetes, including cancer, cardiovascular diseases and neurological disorders, represent one of the major ongoing threats to human life, becoming a true pandemic of the 21st century. Current treatment strategies for diabetes mainly involve promoting β-cell differentiation, and one of the most widely studied targets for β-cell regeneration is DYRK1A kinase, a member of the DYRK family. DYRK1A has been characterized as a key regulator of cell growth, differentiation, and signal transduction in various organisms, while further roles and substrates are the subjects of extensive investigation. The targets of interest in this review are implicated in the regulation of β-cells through DYRK1A inhibition—through driving their transition from highly inefficient and death-prone populations into efficient and sufficient precursors of islet regeneration. Increasing evidence for the role of DYRK1A in diabetes progression and β-cell proliferation expands the potential for pharmaceutical applications of DYRK1A inhibitors. The variety of new compounds and binding modes, determined by crystal structure and in vitro studies, may lead to new strategies for diabetes treatment. This review provides recent insights into the initial self-activation of DYRK1A by tyrosine autophosphorylation. Moreover, the importance of developing novel DYRK1A inhibitors and their implications for the treatment of diabetes are thoroughly discussed. The evolving understanding of DYRK kinase structure and function and emerging high-throughput screening technologies have been described. As a final point of this work, we intend to promote the term “diabetic kinome” as part of scientific terminology to emphasize the role of the synergistic action of multiple kinases in governing the molecular processes that underlie this particular group of diseases.

show abstract

Review of β‐carboline and its derivatives as selective MAO‐A inhibitors

Benny

Jayan

Abdelgawad

et al. 2023

Archiv der Pharmazie

View full text Add to dashboard Cite

As flavin adenine dinucleotide (FAD)-dependent enzymes, monoamine oxidases (MAOs) catalyze the oxidative deamination of various endogenous and exogenous amines. MAO-A inhibitors are thought to be effective therapeutic agents for treating neurological diseases including depression and anxiety. Due to the academic challenge of developing new human (h) MAO-A inhibitors and the potential for discovering substances with remarkable properties compared to existing MAO-A inhibitors, numerous research groups are looking into novel classes of chemical compounds that may function as selective hMAO-A inhibitors. β-Carbolines are reported to be a prominent class of bioactive molecules exhibiting MAO-A inhibition. Chemically, β-carboline is a tricyclic pyrido-3,4-indole ring. It has only recently been discovered that this chemotype has highly effective and specific MAO-A inhibitory activity. In this review, structure-activity relationship studies included in particular research publications from the 1960s to the present are discussed with regard to β-carboline and its analogs. This comprehensive information helps to design and develop a new family of MAO-A inhibitors for the management of depressive disorders.

show abstract

Identification of harmine and β-carboline analogs from a high-throughput screen of an approved drug collection; profiling as differential inhibitors of DYRK1A and monoamine oxidase A and for in vitro and in vivo anti-cancer studies

Cited by 28 publications

References 115 publications

Data supporting a pilot high-throughput screen of a drug library for identification of DYRK1A inhibitors and high-content imaging analysis of identified harmine analogs

Data supporting a pilot high-throughput screen of a drug library for identification of DYRK1A inhibitors and high-content imaging analysis of identified harmine analogs

Diabetic Kinome Inhibitors—A New Opportunity for β-Cells Restoration

Review of β‐carboline and its derivatives as selective MAO‐A inhibitors

Contact Info

Product

Resources

About