Author(s): Sangeeta Mahaur, Sukirti Upadhyay, Ravi Raj Pal

Email(s): , ,

DOI: 10.5958/2321-5836.2020.00028.2   

Address: Sangeeta Mahaur 1*, Dr. Sukirti Upadhyay2, Ravi Raj Pal3
1Department of Pharmaceutical Sciences, IFTM University, Moradabad, 244001, U. P. India.
2Associate Professor, Department of Pharmaceutical Sciences, IFTM University, Moradabad, 244001, U. P. India.
3Dyaynand Dinanath College, Institute of Pharmacy, National Highway 86, Ramaipur, Kanpur, Uttar Pradesh 209214, U.P. India.
*Corresponding Author

Published In:   Volume - 12,      Issue - 4,     Year - 2020

Unusual and rapid reproductions of oncogene BCR-ABL protein in the stem cells has been established as the major cause of Chronic Myeloid Leukemia. It has been recognized that tyrosine kinase province of BCR-ABL protein is a possible healing target for the action of Chronic Myeloid Leukemia. First generation drug Imatinib could impede the enzymatic action by impeding the ATP binding with BCR-ABL protein. Second generation drugs Bosutinib, Nilotinib, Dasatinib, Ponatinib, Bafetinib can also against the mutated province of ABL tyrosine kinase protein. The purpose of the present study was to virtually screen the Indolizine databases compound library downloaded. The structure-based virtual screening on BCR-ABL was downloaded from protein data bank. The exhaustive docking approach on BCR-ABL has been performed using simple precision and extra precision mode and the findings of most potent compounds have been evaluated for their absorption, distribution, metabolism and excretion.

Cite this article:
Sangeeta Mahaur, Sukirti Upadhyay, Ravi Raj Pal. Indolizine: In-Silico Identification of Inhibitors against Mutated BCR-ABL Protein of Chronic Myeloid Leukemia. Res. J. Pharmacology and Pharmacodynamics.2020; 12(4):151-158. doi: 10.5958/2321-5836.2020.00028.2

1.    Andrews, M. J. I., et al. (2011). Imidazolopyrazine compounds useful for the treatment of degenerative and inflammatory diseases, Google Patents.
2.    Azam, M. and M. Kesarwani (2017). Therapy for solid tumors, Google Patents.
3.    Banavath, H. N., et al. (2014). "Identification of novel tyrosine kinase inhibitors for drug resistant T315I mutant BCR-ABL: a virtual screening and molecular dynamics simulations study." Scientific reports4: 6948.
4.    Bedi, A., et al. (1994). "Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia." Blood83 (8): 2038-2044.
5.    Druker, B. J., et al. (2001). "Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia." New England Journal of Medicine344 (14): 1031-1037.
6.    Dubey, K. D. and R. P. Ojha (2011). "Conformational flexibility and binding energy profile of c-Abl tyrosine kinase complexed with Imatinib: an insight from MD study." Molecular Simulation37 (14): 1151-1163.
7.    Gudimetla, K., et al. (2020). "Review on Pathophysiological and Pharmacotherapeutic approach on Chronic Myeloid Leukemia." Research Journal of Pharmacy and Technology13(6): 2971-2976.
8.    Hägerkvist, R. and N. Welsh (2007). Use of tyrosine kinase inhibitor to treat diabetes, Google Patents.
9.    Ho, H. K., et al. (2014). "Current strategies for inhibiting FGFR activities in clinical applications: opportunities, challenges and toxicological considerations." Drug discovery today19(1): 51-62.
10.    Huisman, G. W., et al. (2018). Imidazoyl anilide derivatives and methods of use, US Patent App. 15/504,134.
11.    Karale, P. A., et al. (2018). "Advanced Molecular Targeted Therapy in Breast Cancer." Research Journal of Pharmacology and Pharmacodynamics10(1): 29-37.
12.    Kralovics, R., et al. (2005). "A gain-of-function mutation of JAK2 in myeloproliferative disorders." New England Journal of Medicine352(17): 1779-1790.
13.    Kumar, H., et al. (2015). "Systemic review on chronic myeloid leukemia: therapeutic targets, pathways and inhibitors." J Nucl Med Radiat Ther6 (6).
14.    Malik, R., et al. (2016). "High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents." Journal of Molecular Structure1122: 239-246.
15.    Nagwanshi, P., et al. (2020). "Emphasis of Phytoconstituent in the treatment of cancer." Research Journal of Pharmaceutical Dosage Forms and Technology12(3): 169-177.
16.    Pandey, R. K., et al. (2017). "Exploring dual inhibitory role of febrifugine analogues against Plasmodium utilizing structure-based virtual screening and molecular dynamic simulation." Journal of Biomolecular Structure and Dynamics35 (4): 791-804.
17.    Pane, F., et al. (1996). "Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction)[see comments]." Blood88 (7): 2410-2414.
18.    Preisinger, C., et al. (2013). "Imatinib-dependent tyrosine phosphorylation profiling of Bcr-Abl-positive chronic myeloid leukemia cells." Leukemia27 (3): 743.
19.    Quintás‐Cardama, A., et al. (2009). "Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009." Cancer115 (23): 5382-5393.
20.    Reckel, S., et al. (2017). "Differential signaling networks of Bcr–Abl p210 and p190 kinases in leukemia cells defined by functional proteomics." Leukemia31 (7): 1502.
21.    Rodgers, J. D., et al. (2014). Metabolites of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo [2, 3-d] pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile, Google Patents.
22.    Rodgers, J. D., et al. (2010). Metabolites of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo [2, 3-d] pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile, Google Patents.
23.    Saxty, G., et al. (2011). Bicyclic heterocyclic compounds as protein tyrosine kinase inhibitors, Google Patents.
24.    Soni, A., et al. (2017). "In-vitro cytotoxic activity of plant saponin extracts on breast cancer cell-line." Research Journal of Pharmacognosy and Phytochemistry9 (1): 17-22.
25.    Sudhakar, P. (2017). Molecular Docking and Synthesis of 1, 2, 4-Triazin Analogue of Diclofenac as Potential Ligand for Chlorpromazine Induced Parkinson’s in Rat Model, Swamy Vivekanandha College of Pharmacy, Tiruchengode.
26.    Sudhakar, P., et al. (2018). "Molecular docking and synthesis of 1, 2, 4-triazin analogue of diclofenac as potential ligand for parkinson's." Research Journal of Pharmacology and Pharmacodynamics10 (1): 8-12.

27.    Vintonyak, V. V., et al. (2011). "Using small molecules to target protein phosphatases." Bioorganic and medicinal chemistry19(7): 2145-2155.
28.    Weisberg, E., et al. (2006). "AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL." British journal of cancer94(12): 1765.
29.    Zhou, F., et al. (2017). "A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case." Molecular cytogenetics10(1): 19.

Recomonded Articles:

Research Journal of Pharmacology and Pharmacodynamics (RJPPD) is an international, peer-reviewed journal....... Read more >>>

RNI: Not Available                     
DOI: 10.5958 2321-5836 

Recent Articles