International Journal of Research in Pharmacy and Allied Science

ISSN: 2583-6544   |  Issues per year: Monthly  |   Indexed In: Google Scholar, CORE, ScienceOpen, Researchgate

ISSN:2583-6544

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Targeting Key Signalling Pathways in Leukemia: A Docking-Based Approach for Drug Discovery

Author(s): Fadilullahi Opeyemi Ibiyemi*1, Ismail Kolawole Odetayo2

Email(s): 1ibiyemi.ademola97@gmail.com

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    1Department of Chemistry & Industrial Chemistry, Osun State Water Regulatory Commission, Ministry of Water Resources , Osun State, Nigeria 2Department of Biochemistry & Chemistry Fountain University, P.M.B. 4491 Osogbo Osun State, Nigeria

Published In:   Volume - 4,      Issue - 8,     Year - 2025

DOI: https://doi.org/10.71431/IJRPAS.2025.4806  

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ABSTRACT:
Cancer may be a sort of malady that bargains with advancement and multiplication of irregular cell, they have inclination to devastate typical cell. The aim of this research is to conduct a comprehensive review of key signaling pathways implicated in leukemia progression and to identify potential molecular targets, finally to perform molecular docking simulations to predict the binding affinities and interactions between selected ligands and target proteins. This investigate is centered on leukemia which is the cancer of the blood cell, caused by protein FLT3 gene, which we have targeted the signal pathway in leukemia using a docking based approach for drug discovery. In this thinks about, assortments of phytoconstituent were chosen selected, to check their liking for treating leukemia and the phytoconstituent were chosen on the criterial of lipkins rule and preADMET for ADME and toxicology prediction. The chosen phytoconstituent were associating with protein causing leukemia FLT3 (1ETE) utilizing schrodinger maestro software program to perform the docking.Result shows that resveratrol and pterostilbene shows a better docking score after the protein-ligand interaction with a binding score of -5.606 and -5.218 respectively, which underscores the potential of resveratrol and pterostilbene as a good candidate for inhibiting FLT3 gene causing leukemia compare to other selected phytoconstituent.

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Cite this article:
Fadilullahi Opeyemi Ibiyemi, Ismail Kolawole Odetayo. Targeting Key Signalling Pathways in Leukemia: A Docking-Based Approach for Drug Discovery. IJRPAS, August 2025; 4 (8)79-99.DOI: https://doi.org/https://doi.org/10.71431/IJRPAS.2025.4806


    Abohassan M, Alshahrani M, Alshahrani MY, Rajagopalan P. Insilco and Invitro approaches identify novel dual PI3K/AKT pathway inhibitors to control acute myeloid leukemia cell proliferations. Medical Oncology. 2022 Oct 8;39(12):249.

2.      Adelusi, T. I., Oyedele, A. K., Abdeen, I. D.B., Ogunlana, T., Adeyemi, R. O., Ukachi, C. D., Idris, M. O., Olaoba, O. T., Adedotun, I. O., Kolawole, O. E., Xiaoxing, Y., Abdul-Hammed, M.. (2022). Molecular modeling in drug discovery. Informatics Medicine Unlocked, 29, 100880. https://doi.org/10.1016/J.IMU.2022.100880

3.      American Physiological Society. (2019). FMS-like tyrosine kinase 3/FLT3: From basic science to clinical implications. https://journals.physiology.org/doi/full/10.1152/physrev.00029.2018

4.      Arthur DE, Uzairu A. Molecular docking studies on the interaction of NCI anticancer analogues with human Phosphatidylinositol 4, 5-bisphosphate 3-kinase catalytic subunit. Journal of King Saud University-Science. 2019 Oct 1;31(4):1151-66.

5.      Audrito V, Vaisitti T, Rossi D, et al. Nicotinamide blocks proliferation and induces apoptosis of chronic lymphocytic leukemia cells through activation of the p53/miR-34a/SIRT1 tumor suppressor network. Cancer Res. 2011;71:4473–83.

6.      Bajbouj K, Shafarin J, Hamad M. High-dose deferoxamine treatment disrupts intracellular Iron homeostasis, reduces growth, and induces apoptosis in metastatic and nonmetastatic breast cancer cell lines. Technol Cancer Res Treat. 2018;17:1533033818764470.

7.      Barrett T, Troup DB, Wilhite SE, et al. NCBI GEO: mining tens of millions of expression profiles--database and tools update. Nucleic Acids Res. 2007;35:D760–5.

8.      Becker S. A historic and scientific review of breast cancer: The next global healthcare challenge. International Journal of Gynecology & Obstetrics. 2015 Oct;131:S36-9.

9.      Chattaraj, P. K., & Giri, S. (2007). Stability, Reactivity, and Aromaticity of Compounds of a Multivalent Superatom. The Journal of Physical Chemistry. A, 111(43), 11116–11121. https://doi.org/10.1021/JP0760758

10.  Choudhary, M. I., Shaikh, M., Tul-Wahab, A., & Ur-Rahman, A. (2020). In silico identification of potential inhibitors of key SARS-CoV-2 3CL hydrolase (Mpro) via molecular docking, MMGBSA predictive binding energy calculations, and molecular dynamics simulation. PloS One, 15(7), e0235030. https://doi.org/10.1371/journal.pone.0235030

11.  Davis AS, Viera AJ, Mead MD. Leukemia: an overview for primary care. American family physician. 2014 May 1;89(9):731-8.

12.  Del Prado-Audelo ML, Cortes H, Caballero-Floran IH, Gonzalez-Torres M, Escutia-Guadarrama L, et al. Therapeutic applications of terpenes on inflammatory diseases. Frontiers in Pharmacology, (2021); 12: 704197.

13.  Egbuna C, Patrick-Iwuanyanwu KC, Onyeike EN, Khan J, Alshehri B. FMS-like tyrosine kinase-3 (FLT3) inhibitors with better binding affinity and ADMET properties than sorafenib and gilteritinib against acute myeloid leukemia: in silico studies. Journal of Biomolecular Structure and Dynamics. 2022 Dec 12;40(22):12248-59.

14.  Fan M, Yuan S, Li L, Zheng J, Zhao D, et al. Application of terpenoid compounds in food and pharmaceutical products. Fermentation, (2023); 9(2): 119.

15.  Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood, The Journal of the American Society of Hematology. 2002 Sep 1;100(5):1532-42.

16.  Gilliland DG, Jordan CT, Felix CA. The molecular basis of leukemia. ASH Education Program Book. 2004 Jan 1;2004(1):80-97.

17.  Gokhale P, Chauhan AP, Arora A, Khandekar N, Nayarisseri A, Singh SK. FLT3 inhibitor design using molecular docking based virtual screening for acute myeloid leukemia. Bioinformation. 2019;15(2):104.

18.  Grove CS, Vassiliou GS. Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer? Dis Model Mech. 2014;7:941–51.

19.  Helmi N. Identification of therapeutic phytochemicals targeting B-cell lymphoma 2 (BCL2) as anti-acute myeloid leukemia agents: An in-silico approach. Advancements in Life Sciences. 2024 Jan 8;10(4):670-4.

20.  Islam MR, Osman OI, Hassan WM. Identifying novel therapeutic inhibitors to target FMS-like tyrosine kinase-3 (FLT3) against acute myeloid leukemia: a molecular docking, molecular dynamics, and DFT study. Journal of Biomolecular Structure and Dynamics. 2024 Jan 2;42(1):82-100.

21.  Kampen KR. The discovery and early understanding of leukemia. Leukemia research. 2012 Jan 1;36(1):6-13.

22.  Kiyoi H, Yanada M, Ozekia K. Clinical significance of FLT3 in leukemia. International journal of hematology. 2005 Aug;82:85-92.

23.  Kiyoi, H. and Naoe, T., 2002. FLT3 in human hematologic malignancies. Leukemia & lymphoma, 43(8), pp.1541-1547.

24.  Kuchenbauer F, Kern W, Schoch C, Kohlmann A, Hiddemann W, Haferlach T, Schnittger S. Detailed analysis of FLT3 expression levels in acute myeloid leukemia. Haematologica. 2005 Jan 1;90(12):1617-25.

25.  Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013?. Hematology 2013, the American Society of Hematology Education Program Book. 2013 Dec 6;2013(1):220-6.

26.  Levis M, Small D. FLT3: ITDoes matter in leukemia. Leukemia. 2003 Sep;17(9):1738-52.

27.  Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. New England Journal of Medicine. 1999 Sep 30;341(14):1051-62.

28.  Mirza Z, Karim S. Structure-Based Profiling of Potential Phytomolecules with AKT1 a Key Cancer Drug Target. Molecules. 2023 Mar 13;28(6):2597.

29.  Natarajan A, Thangarajan R, Kesavan S. Repurposing Drugs by In Silico Methods to Target BCR Kinase Domain in Chronic Myeloid Leukemia. Asian Pacific Journal of Cancer Prevention: APJCP. 2019;20(11):3399.

30.  Ozeki K, Kiyoi H, Hirose Y, Iwai M, Ninomiya M, Kodera Y, Miyawaki S, Kuriyama K, Shimazaki C, Akiyama H, Nishimura M. Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia. Blood. 2004 Mar 1;103(5):1901-8.

31.  Parker SK, Williams HM, Turner N. Modeling the antecedents of proactive behavior at work. Journal of applied psychology. 2006 May;91(3):636.

32.  Pei H, Guo W, Peng Y, Xiong H, Chen Y. Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective. Medicinal Research Reviews. 2022 Jul;42(4):1607-60.

33.  Primavera E, Palazzotti D, Barreca ML, Astolfi A. Computer-Aided Identification of Kinase-Targeted Small Molecules for Cancer: A Review on AKT Protein. Pharmaceuticals. 2023 Jul 11;16(7):993.

34.  Quentmeier H, Reinhardt J, Zaborski M, Drexler HG. FLT3 mutations in acute myeloid leukemia cell lines. Leukemia. 2003 Jan;17(1):120-4.

35.  Rombouts WJ, Blokland I, Löwenberg B, Ploemacher RE. Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia. 2000 Apr;14(4):675-83.

36.  Singh VK, Chang HH, Kuo CC, Shiao HY, Hsieh HP, Coumar MS. Drug repurposing for chronic myeloid leukemia: in silico and in vitro investigation of DrugBank database for allosteric Bcr-Abl inhibitors. Journal of Biomolecular Structure and Dynamics. 2017 Jun 11;35(8):1833-48.

37.  Small D. FLT3 mutations: biology and treatment. ASH Education Program Book. 2006 Jan 1;2006(1):178-84.

38.  Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nature Reviews Cancer. 2003 Sep 1;3(9):650-65.

39.  Sabe VT, Ntombela T, Jhamba LA, Maguire GEM, Govender T, et al. Current trends in computer aided drug design and a highlight of drugs discovered via computational techniques: A review. European Journal of Medicinal Chemistry, (2021); 224: 113705.

40.  Sweta J, Khandelwal R, Srinitha S, Pancholi R, Adhikary R, Ali MA, Nayarisseri A, Vuree S, Singh SK. Identification of high-affinity small molecule targeting IDH2 for the clinical treatment of acute myeloid leukemia. Asian Pacific journal of cancer prevention: APJCP. 2019;20(8):2287.

41.  Usha T, Shanmugarajan D, Goyal AK, Kumar CS, Middha SK. Recent Updates on Computer-aided Drug Discovery: Time for a Paradigm Shift. Current Topics in Medicinal Chemistry, (2017); 17(30): 3296-3307.

42.  Wang Y, Wu X, Ren Z, Li Y, Zou W, Chen J, Wang H. Overcoming cancer chemotherapy resistance by the induction of ferroptosis. Drug Resistance Updates. 2023 Jan 1;66:100916.

43.  Yang Y, Yang Y, Shen Y, Liu J, Zeng Y, Wei C, Liu C, Pan Y, Guo Q, Zhong F, Guo L. Exploring the pharmacological mechanisms of Shuanghuanglian against T-cell acute lymphoblastic leukaemia through network pharmacology combined with molecular docking and experimental validation. Pharmaceutical biology. 2023 Dec 31;61(1):259-70.

44.  Zhang S, Sun K, Zheng R, Zeng H, Wang S, Chen R, Wei W, He J. Cancer incidence and mortality in China, 2015. Journal of the National Cancer Center. 2021 Mar 1;1(1):2-11.

 

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