Research Article


DOI :10.26650/experimed.1358971   IUP :10.26650/experimed.1358971    Full Text (PDF)

Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach

Cansu ErgunBuse Zeren KiremitçiGizem ArslantaşBusenur BozkurtGizem Ayna DuranYağmur Kiraz

Objective: Acute myeloid leukemia (AML) is a malignant disease characterized by the uncontrolled growth, differentiation, and proliferation of immature hematopoietic cells. Patients with AML often have poor survival rates, which are associated with specific gene mutations in FLT3, CEBPA, and NPM1. The phosphatidylinositol 3-kinase (PI3K) pathway, a lipase pathway, is activated in many malignancies, including AML. Given the low survival rates in AML, this study identified candidate drugs that could inhibit the PI3K pathway, thereby offering a potential treatment for AML, by using a drug-repurposing approach.

Materials and Methods: Online bioinformatics tools were utilized to identify pathway-related genes and FDA-approved drugs. Subsequently, molecular docking was performed to determine the binding affinity values. Important genes were identified by evaluating their impact on survival and their aberrant expression in the tumor. In this study, genes such as VAV1, GSK3B, MTOR, PDPK1, PRR5, TSC2, AKT3, and CREB1 were determined and docked with their potential inhibitors. Particular attention was paid to VAV1 because there were no known potential VAV1 inhibitors used in AML.

Results: The docking results were ranked, and the proposed gene–drug pairs were identified as tideglusib and fostamatinib for the inhibition of GSK3B, pimecrolimus and fostamatinib for the inhibition of MTOR, and fostamatinib for the inhibition of PDPK1. Furthermore, nebivolol, darifenacin, dihydroergotamine, libanserin and entereg were identified as potential inhibitors of VAV1 in AML.

Conclusion: To sum up, most effective gene–drug pairs according to binding affinities were proposed as candidate inhibitor drugs for AML.


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APA

Ergun, C., Kiremitçi, B.Z., Arslantaş, G., Bozkurt, B., Ayna Duran, G., & Kiraz, Y. (2023). Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach. Experimed, 13(3), 205-212. https://doi.org/10.26650/experimed.1358971


AMA

Ergun C, Kiremitçi B Z, Arslantaş G, Bozkurt B, Ayna Duran G, Kiraz Y. Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach. Experimed. 2023;13(3):205-212. https://doi.org/10.26650/experimed.1358971


ABNT

Ergun, C.; Kiremitçi, B.Z.; Arslantaş, G.; Bozkurt, B.; Ayna Duran, G.; Kiraz, Y. Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach. Experimed, [Publisher Location], v. 13, n. 3, p. 205-212, 2023.


Chicago: Author-Date Style

Ergun, Cansu, and Buse Zeren Kiremitçi and Gizem Arslantaş and Busenur Bozkurt and Gizem Ayna Duran and Yağmur Kiraz. 2023. “Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach.” Experimed 13, no. 3: 205-212. https://doi.org/10.26650/experimed.1358971


Chicago: Humanities Style

Ergun, Cansu, and Buse Zeren Kiremitçi and Gizem Arslantaş and Busenur Bozkurt and Gizem Ayna Duran and Yağmur Kiraz. Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach.” Experimed 13, no. 3 (Mar. 2024): 205-212. https://doi.org/10.26650/experimed.1358971


Harvard: Australian Style

Ergun, C & Kiremitçi, BZ & Arslantaş, G & Bozkurt, B & Ayna Duran, G & Kiraz, Y 2023, 'Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach', Experimed, vol. 13, no. 3, pp. 205-212, viewed 5 Mar. 2024, https://doi.org/10.26650/experimed.1358971


Harvard: Author-Date Style

Ergun, C. and Kiremitçi, B.Z. and Arslantaş, G. and Bozkurt, B. and Ayna Duran, G. and Kiraz, Y. (2023) ‘Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach’, Experimed, 13(3), pp. 205-212. https://doi.org/10.26650/experimed.1358971 (5 Mar. 2024).


MLA

Ergun, Cansu, and Buse Zeren Kiremitçi and Gizem Arslantaş and Busenur Bozkurt and Gizem Ayna Duran and Yağmur Kiraz. Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach.” Experimed, vol. 13, no. 3, 2023, pp. 205-212. [Database Container], https://doi.org/10.26650/experimed.1358971


Vancouver

Ergun C, Kiremitçi BZ, Arslantaş G, Bozkurt B, Ayna Duran G, Kiraz Y. Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach. Experimed [Internet]. 5 Mar. 2024 [cited 5 Mar. 2024];13(3):205-212. Available from: https://doi.org/10.26650/experimed.1358971 doi: 10.26650/experimed.1358971


ISNAD

Ergun, Cansu - Kiremitçi, BuseZeren - Arslantaş, Gizem - Bozkurt, Busenur - Ayna Duran, Gizem - Kiraz, Yağmur. Exploring PI3K Pathway Inhibitors for Acute Myeloid Leukemia: A Drug-Repurposing Approach”. Experimed 13/3 (Mar. 2024): 205-212. https://doi.org/10.26650/experimed.1358971



TIMELINE


Submitted19.09.2023
Accepted01.11.2023
Published Online28.12.2023

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